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The US Drug Enforcement Agency (DEA) is moving forward with plans to move marijuana from a Schedule I to a Schedule III controlled substance under the Controlled Substance Act (CSA), the US Department of Justice officials announced this week. 

First reported by the Associated Press and since confirmed by this news organization through a US Department of Justice spokesperson, the news made international headlines. Despite the media splash, the final rule is still months away.

How did we get here? What happens next? What impact might rescheduling have on clinicians, patients, researchers, and the medical cannabis industry? 

Why Reschedule? Why Now? 

The DEA’s decision is based on a 2023 determination from the US Food and Drug Administration (FDA) that marijuana has a legitimate medical use and should be moved to Schedule III. 

DEA defines Schedule I drugs as those with no currently accepted medical use and a high potential for abuse. That class includes heroin, LSD, and ecstasy. Schedule III drugs have a moderate to low potential for physical and psychological dependence and have a currently accepted medical use. This class includes ketamine, acetaminophen with codeine, and buprenorphine. 

Even though the manufacturing, distribution, sale, and use of marijuana has long violated federal law, 38 states and Washington, DC, have legalized medical cannabis, and 24 states and DC have legalized its recreational use.

Congress has allowed states leeway for the distribution and use of medical marijuana, and current and previous presidential administrations have chosen not to aggressively pursue prosecution of state-allowed marijuana use, the Congressional Research Service (CRS) reports. 

Pressure to address the conflict between federal and state laws and an increasing interest in drug development of cannabis and cannabis-derived products probably contributed to the DEA’s decision, said Stephen Strakowski, MD, professor, and vice chair of psychiatry at Indiana University in Indianapolis, and professor and associate vice president at University of Texas in Austin.

“The trend toward legalization is everywhere and even though nationally the feds in this instance are lagging the states, the pressure to legalize has been intense for 50 years and it’s not surprising that the DEA is finally following that lead,” Dr. Strakowski told this news organization. 

How Does Rescheduling Work? What’s the Timeline?

The DEA will submit a formal rule proposing that marijuana be moved from Schedule I to Schedule III to the White House Office of Management and Budget. The timing of the submission is unclear. 

Once the proposed rule is posted to the Federal Register, there will be a public comment period, which usually lasts 30-60 days.

“This will likely generate a lot of public comment,” Robert Mikos, JD, LaRoche Family Chair in Law at Vanderbilt University Law School in Nashville, Tennessee, told this news organization. “Then the agency has to go back and wade through those comments and decide if they want to proceed with the rule as proposed or modify it.”

A final rule will probably be posted before the end of the current presidential term in January, Mr. Mikos said. While a lawsuit blocking its implementation is possible, there is a “low chance that a court would block this,” he added.

How Will Rescheduling Affect Medical Marijuana?

For medical marijuana, changing the drug to a Schedule III means that it can legally be prescribed but only in states that have legalized medical cannabis, Mr. Mikos said. 

“If you’re a patient in a state with a medical marijuana law and your physician gives you a prescription for medical marijuana and you possess it, you will no longer be guilty of a federal crime,” he said.

Rescheduling could also benefit patients who receive care through the Veterans Administration (VA), Mr. Mikos said. For several years, the VA has had a policy that blocked clinicians from prescribing medical marijuana because as a Schedule I drug, it was determined to have no accepted medical use. 

“It’s possible the VA may drop that policy once the drug gets rescheduled. If you’re in a medical marijuana state, if you’re a VA patient, and you don’t want to spend the extra money to go outside that system, this will have meaningful impact on their lives,” Mr. Mikos said.

But what about patients living in states that have not legalized medical cannabis? 

“You still wouldn’t be committing a federal crime, but you could be violating state law,” Mr. Mikos said. “That’s a much more salient consideration because if you look at who goes after individuals who possess small amounts of drugs, the state handles 99% of those cases.” 

The manufacture, distribution, and possession of recreational marijuana would remain illegal under federal law.

What Does It Mean for Medical Marijuana Dispensaries?

Though rescheduling makes it legal for clinicians to prescribe medical marijuana and for patients to use it, the actual sale of the drug will remain illegal under federal law because rescheduling only changes prescribing under the CSA, Mr. Mikos said.

“If you’re a dispensary and you sell it, even if it’s to somebody who’s got a prescription, you’re still probably violating the Food, Drug and Cosmetics Act. Rescheduling doesn’t change that,” he said. 

“Even assuming the DEA follows through with this and it doesn’t come undone at some future date, the industry is still going struggle to comply with the Controlled Substances Act post rescheduling because that statute is going to continue to impose a number of regulations on the industry,” Mr. Mikos added.

However, rescheduling would change the tax status of the estimated 12,000-15,000 state-licensed cannabis dispensaries in the United States, allowing access to certain tax deductions that are unavailable to sales involving Schedule I controlled substances, James Daily, JD, MS, with Center for Empirical Research in the Law at Washington University School of Law in St. Louis, told this news organization.

“Many cannabis businesses do in fact pay federal taxes, but the inability to take any federal tax credits or deductions means that their effective tax rate is much higher than it would otherwise be,” Mr. Daily said. 

Although new federal tax deductions would likely available to cannabis businesses if marijuana were rescheduled to Schedule III, “their business would still be in violation of federal law,” he said. 

“This creates a further tension between state and federal law, which could be resolved by further legalization or it could be resolved by extending the prohibition on tax deductions to include cannabis and not just Schedule I and II drugs,” he added.

Will Rescheduling Make It Easier to Conduct Cannabis-Related Research? 

Research on medical cannabis has been stymied by FDA and DEA regulations regarding the study of Schedule I controlled substances. Although rescheduling could lift that barrier, other challenges would remain.

“Schedule III drugs can be more easily researched, but it’s unclear if, for example, a clinical trial could lawfully obtain the cannabis from a dispensary or if they would still have to go through the one legal federal supplier of cannabis,” Daily said. 

The FDA reports having received more than 800 investigational new drug applications for and pre-investigational new drug applications related to cannabis and cannabis-derived products since the 1970s, the agency reports. To date, the FDA has not approved any marketing drug applications for cannabis for the treatment of any disease or condition. 

In January 2023, the agency published updated guidelines for researchers and sponsors interested in developing drugs containing cannabis or cannabis-derived compounds. 

It’s unclear whether those guidelines would be updated if the rescheduling moves forward. 

Does Rescheduling Marijuana Pose Any Risk? 

In its report to the DEA that marijuana be rescheduled, the FDA was careful to note that the agency’s recommendation is “not meant to imply that safety and effectiveness have been established for marijuana that would support FDA approval of a marijuana drug product for a particular indication.”

That’s a notation that clinicians and patients should take to heart, Dr. Strakowski said. 

“It’s important to remind people that Schedule III drugs, by definition, have addiction and other side effect risks,” he said. “The celebrity marketing that sits behind a lot of this is incompletely informed. It’s portrayed as fun and harmless in almost every movie and conversation you see, and we know that’s not true.”

Previous studies have linked cannabis to increased risk for mania, anxiety disorders, and schizophrenia. 

“It is increasingly clear that marijuana use is linked to poor outcomes in people who struggle with mental illness,” Dr. Strakowski said. “We have no evidence that it can help you but there is evidence that it can harm you.”

Dr. Strakowski likens cannabis use to alcohol, which is a known depressant that is associated with worse outcomes in people with mental illness. 

“I think with cannabis, we don’t know enough about it yet, but we do know that it does have some anxiety risks,” he said. “The risks in people with mental illness are simply different than in people who don’t have mental illness.”

Dr. Strakowski, Mr. Mikos, and Mr. Daily report no relevant disclosures. 
 

A version of this article appeared on Medscape.com.

The US Drug Enforcement Agency (DEA) is moving forward with plans to move marijuana from a Schedule I to a Schedule III controlled substance under the Controlled Substance Act (CSA), the US Department of Justice officials announced this week. 

First reported by the Associated Press and since confirmed by this news organization through a US Department of Justice spokesperson, the news made international headlines. Despite the media splash, the final rule is still months away.

How did we get here? What happens next? What impact might rescheduling have on clinicians, patients, researchers, and the medical cannabis industry? 

Why Reschedule? Why Now? 

The DEA’s decision is based on a 2023 determination from the US Food and Drug Administration (FDA) that marijuana has a legitimate medical use and should be moved to Schedule III. 

DEA defines Schedule I drugs as those with no currently accepted medical use and a high potential for abuse. That class includes heroin, LSD, and ecstasy. Schedule III drugs have a moderate to low potential for physical and psychological dependence and have a currently accepted medical use. This class includes ketamine, acetaminophen with codeine, and buprenorphine. 

Even though the manufacturing, distribution, sale, and use of marijuana has long violated federal law, 38 states and Washington, DC, have legalized medical cannabis, and 24 states and DC have legalized its recreational use.

Congress has allowed states leeway for the distribution and use of medical marijuana, and current and previous presidential administrations have chosen not to aggressively pursue prosecution of state-allowed marijuana use, the Congressional Research Service (CRS) reports. 

Pressure to address the conflict between federal and state laws and an increasing interest in drug development of cannabis and cannabis-derived products probably contributed to the DEA’s decision, said Stephen Strakowski, MD, professor, and vice chair of psychiatry at Indiana University in Indianapolis, and professor and associate vice president at University of Texas in Austin.

“The trend toward legalization is everywhere and even though nationally the feds in this instance are lagging the states, the pressure to legalize has been intense for 50 years and it’s not surprising that the DEA is finally following that lead,” Dr. Strakowski told this news organization. 

How Does Rescheduling Work? What’s the Timeline?

The DEA will submit a formal rule proposing that marijuana be moved from Schedule I to Schedule III to the White House Office of Management and Budget. The timing of the submission is unclear. 

Once the proposed rule is posted to the Federal Register, there will be a public comment period, which usually lasts 30-60 days.

“This will likely generate a lot of public comment,” Robert Mikos, JD, LaRoche Family Chair in Law at Vanderbilt University Law School in Nashville, Tennessee, told this news organization. “Then the agency has to go back and wade through those comments and decide if they want to proceed with the rule as proposed or modify it.”

A final rule will probably be posted before the end of the current presidential term in January, Mr. Mikos said. While a lawsuit blocking its implementation is possible, there is a “low chance that a court would block this,” he added.

How Will Rescheduling Affect Medical Marijuana?

For medical marijuana, changing the drug to a Schedule III means that it can legally be prescribed but only in states that have legalized medical cannabis, Mr. Mikos said. 

“If you’re a patient in a state with a medical marijuana law and your physician gives you a prescription for medical marijuana and you possess it, you will no longer be guilty of a federal crime,” he said.

Rescheduling could also benefit patients who receive care through the Veterans Administration (VA), Mr. Mikos said. For several years, the VA has had a policy that blocked clinicians from prescribing medical marijuana because as a Schedule I drug, it was determined to have no accepted medical use. 

“It’s possible the VA may drop that policy once the drug gets rescheduled. If you’re in a medical marijuana state, if you’re a VA patient, and you don’t want to spend the extra money to go outside that system, this will have meaningful impact on their lives,” Mr. Mikos said.

But what about patients living in states that have not legalized medical cannabis? 

“You still wouldn’t be committing a federal crime, but you could be violating state law,” Mr. Mikos said. “That’s a much more salient consideration because if you look at who goes after individuals who possess small amounts of drugs, the state handles 99% of those cases.” 

The manufacture, distribution, and possession of recreational marijuana would remain illegal under federal law.

What Does It Mean for Medical Marijuana Dispensaries?

Though rescheduling makes it legal for clinicians to prescribe medical marijuana and for patients to use it, the actual sale of the drug will remain illegal under federal law because rescheduling only changes prescribing under the CSA, Mr. Mikos said.

“If you’re a dispensary and you sell it, even if it’s to somebody who’s got a prescription, you’re still probably violating the Food, Drug and Cosmetics Act. Rescheduling doesn’t change that,” he said. 

“Even assuming the DEA follows through with this and it doesn’t come undone at some future date, the industry is still going struggle to comply with the Controlled Substances Act post rescheduling because that statute is going to continue to impose a number of regulations on the industry,” Mr. Mikos added.

However, rescheduling would change the tax status of the estimated 12,000-15,000 state-licensed cannabis dispensaries in the United States, allowing access to certain tax deductions that are unavailable to sales involving Schedule I controlled substances, James Daily, JD, MS, with Center for Empirical Research in the Law at Washington University School of Law in St. Louis, told this news organization.

“Many cannabis businesses do in fact pay federal taxes, but the inability to take any federal tax credits or deductions means that their effective tax rate is much higher than it would otherwise be,” Mr. Daily said. 

Although new federal tax deductions would likely available to cannabis businesses if marijuana were rescheduled to Schedule III, “their business would still be in violation of federal law,” he said. 

“This creates a further tension between state and federal law, which could be resolved by further legalization or it could be resolved by extending the prohibition on tax deductions to include cannabis and not just Schedule I and II drugs,” he added.

Will Rescheduling Make It Easier to Conduct Cannabis-Related Research? 

Research on medical cannabis has been stymied by FDA and DEA regulations regarding the study of Schedule I controlled substances. Although rescheduling could lift that barrier, other challenges would remain.

“Schedule III drugs can be more easily researched, but it’s unclear if, for example, a clinical trial could lawfully obtain the cannabis from a dispensary or if they would still have to go through the one legal federal supplier of cannabis,” Daily said. 

The FDA reports having received more than 800 investigational new drug applications for and pre-investigational new drug applications related to cannabis and cannabis-derived products since the 1970s, the agency reports. To date, the FDA has not approved any marketing drug applications for cannabis for the treatment of any disease or condition. 

In January 2023, the agency published updated guidelines for researchers and sponsors interested in developing drugs containing cannabis or cannabis-derived compounds. 

It’s unclear whether those guidelines would be updated if the rescheduling moves forward. 

Does Rescheduling Marijuana Pose Any Risk? 

In its report to the DEA that marijuana be rescheduled, the FDA was careful to note that the agency’s recommendation is “not meant to imply that safety and effectiveness have been established for marijuana that would support FDA approval of a marijuana drug product for a particular indication.”

That’s a notation that clinicians and patients should take to heart, Dr. Strakowski said. 

“It’s important to remind people that Schedule III drugs, by definition, have addiction and other side effect risks,” he said. “The celebrity marketing that sits behind a lot of this is incompletely informed. It’s portrayed as fun and harmless in almost every movie and conversation you see, and we know that’s not true.”

Previous studies have linked cannabis to increased risk for mania, anxiety disorders, and schizophrenia. 

“It is increasingly clear that marijuana use is linked to poor outcomes in people who struggle with mental illness,” Dr. Strakowski said. “We have no evidence that it can help you but there is evidence that it can harm you.”

Dr. Strakowski likens cannabis use to alcohol, which is a known depressant that is associated with worse outcomes in people with mental illness. 

“I think with cannabis, we don’t know enough about it yet, but we do know that it does have some anxiety risks,” he said. “The risks in people with mental illness are simply different than in people who don’t have mental illness.”

Dr. Strakowski, Mr. Mikos, and Mr. Daily report no relevant disclosures. 
 

A version of this article appeared on Medscape.com.

The US Drug Enforcement Agency (DEA) is moving forward with plans to move marijuana from a Schedule I to a Schedule III controlled substance under the Controlled Substance Act (CSA), the US Department of Justice officials announced this week. 

First reported by the Associated Press and since confirmed by this news organization through a US Department of Justice spokesperson, the news made international headlines. Despite the media splash, the final rule is still months away.

How did we get here? What happens next? What impact might rescheduling have on clinicians, patients, researchers, and the medical cannabis industry? 

Why Reschedule? Why Now? 

The DEA’s decision is based on a 2023 determination from the US Food and Drug Administration (FDA) that marijuana has a legitimate medical use and should be moved to Schedule III. 

DEA defines Schedule I drugs as those with no currently accepted medical use and a high potential for abuse. That class includes heroin, LSD, and ecstasy. Schedule III drugs have a moderate to low potential for physical and psychological dependence and have a currently accepted medical use. This class includes ketamine, acetaminophen with codeine, and buprenorphine. 

Even though the manufacturing, distribution, sale, and use of marijuana has long violated federal law, 38 states and Washington, DC, have legalized medical cannabis, and 24 states and DC have legalized its recreational use.

Congress has allowed states leeway for the distribution and use of medical marijuana, and current and previous presidential administrations have chosen not to aggressively pursue prosecution of state-allowed marijuana use, the Congressional Research Service (CRS) reports. 

Pressure to address the conflict between federal and state laws and an increasing interest in drug development of cannabis and cannabis-derived products probably contributed to the DEA’s decision, said Stephen Strakowski, MD, professor, and vice chair of psychiatry at Indiana University in Indianapolis, and professor and associate vice president at University of Texas in Austin.

“The trend toward legalization is everywhere and even though nationally the feds in this instance are lagging the states, the pressure to legalize has been intense for 50 years and it’s not surprising that the DEA is finally following that lead,” Dr. Strakowski told this news organization. 

How Does Rescheduling Work? What’s the Timeline?

The DEA will submit a formal rule proposing that marijuana be moved from Schedule I to Schedule III to the White House Office of Management and Budget. The timing of the submission is unclear. 

Once the proposed rule is posted to the Federal Register, there will be a public comment period, which usually lasts 30-60 days.

“This will likely generate a lot of public comment,” Robert Mikos, JD, LaRoche Family Chair in Law at Vanderbilt University Law School in Nashville, Tennessee, told this news organization. “Then the agency has to go back and wade through those comments and decide if they want to proceed with the rule as proposed or modify it.”

A final rule will probably be posted before the end of the current presidential term in January, Mr. Mikos said. While a lawsuit blocking its implementation is possible, there is a “low chance that a court would block this,” he added.

How Will Rescheduling Affect Medical Marijuana?

For medical marijuana, changing the drug to a Schedule III means that it can legally be prescribed but only in states that have legalized medical cannabis, Mr. Mikos said. 

“If you’re a patient in a state with a medical marijuana law and your physician gives you a prescription for medical marijuana and you possess it, you will no longer be guilty of a federal crime,” he said.

Rescheduling could also benefit patients who receive care through the Veterans Administration (VA), Mr. Mikos said. For several years, the VA has had a policy that blocked clinicians from prescribing medical marijuana because as a Schedule I drug, it was determined to have no accepted medical use. 

“It’s possible the VA may drop that policy once the drug gets rescheduled. If you’re in a medical marijuana state, if you’re a VA patient, and you don’t want to spend the extra money to go outside that system, this will have meaningful impact on their lives,” Mr. Mikos said.

But what about patients living in states that have not legalized medical cannabis? 

“You still wouldn’t be committing a federal crime, but you could be violating state law,” Mr. Mikos said. “That’s a much more salient consideration because if you look at who goes after individuals who possess small amounts of drugs, the state handles 99% of those cases.” 

The manufacture, distribution, and possession of recreational marijuana would remain illegal under federal law.

What Does It Mean for Medical Marijuana Dispensaries?

Though rescheduling makes it legal for clinicians to prescribe medical marijuana and for patients to use it, the actual sale of the drug will remain illegal under federal law because rescheduling only changes prescribing under the CSA, Mr. Mikos said.

“If you’re a dispensary and you sell it, even if it’s to somebody who’s got a prescription, you’re still probably violating the Food, Drug and Cosmetics Act. Rescheduling doesn’t change that,” he said. 

“Even assuming the DEA follows through with this and it doesn’t come undone at some future date, the industry is still going struggle to comply with the Controlled Substances Act post rescheduling because that statute is going to continue to impose a number of regulations on the industry,” Mr. Mikos added.

However, rescheduling would change the tax status of the estimated 12,000-15,000 state-licensed cannabis dispensaries in the United States, allowing access to certain tax deductions that are unavailable to sales involving Schedule I controlled substances, James Daily, JD, MS, with Center for Empirical Research in the Law at Washington University School of Law in St. Louis, told this news organization.

“Many cannabis businesses do in fact pay federal taxes, but the inability to take any federal tax credits or deductions means that their effective tax rate is much higher than it would otherwise be,” Mr. Daily said. 

Although new federal tax deductions would likely available to cannabis businesses if marijuana were rescheduled to Schedule III, “their business would still be in violation of federal law,” he said. 

“This creates a further tension between state and federal law, which could be resolved by further legalization or it could be resolved by extending the prohibition on tax deductions to include cannabis and not just Schedule I and II drugs,” he added.

Will Rescheduling Make It Easier to Conduct Cannabis-Related Research? 

Research on medical cannabis has been stymied by FDA and DEA regulations regarding the study of Schedule I controlled substances. Although rescheduling could lift that barrier, other challenges would remain.

“Schedule III drugs can be more easily researched, but it’s unclear if, for example, a clinical trial could lawfully obtain the cannabis from a dispensary or if they would still have to go through the one legal federal supplier of cannabis,” Daily said. 

The FDA reports having received more than 800 investigational new drug applications for and pre-investigational new drug applications related to cannabis and cannabis-derived products since the 1970s, the agency reports. To date, the FDA has not approved any marketing drug applications for cannabis for the treatment of any disease or condition. 

In January 2023, the agency published updated guidelines for researchers and sponsors interested in developing drugs containing cannabis or cannabis-derived compounds. 

It’s unclear whether those guidelines would be updated if the rescheduling moves forward. 

Does Rescheduling Marijuana Pose Any Risk? 

In its report to the DEA that marijuana be rescheduled, the FDA was careful to note that the agency’s recommendation is “not meant to imply that safety and effectiveness have been established for marijuana that would support FDA approval of a marijuana drug product for a particular indication.”

That’s a notation that clinicians and patients should take to heart, Dr. Strakowski said. 

“It’s important to remind people that Schedule III drugs, by definition, have addiction and other side effect risks,” he said. “The celebrity marketing that sits behind a lot of this is incompletely informed. It’s portrayed as fun and harmless in almost every movie and conversation you see, and we know that’s not true.”

Previous studies have linked cannabis to increased risk for mania, anxiety disorders, and schizophrenia. 

“It is increasingly clear that marijuana use is linked to poor outcomes in people who struggle with mental illness,” Dr. Strakowski said. “We have no evidence that it can help you but there is evidence that it can harm you.”

Dr. Strakowski likens cannabis use to alcohol, which is a known depressant that is associated with worse outcomes in people with mental illness. 

“I think with cannabis, we don’t know enough about it yet, but we do know that it does have some anxiety risks,” he said. “The risks in people with mental illness are simply different than in people who don’t have mental illness.”

Dr. Strakowski, Mr. Mikos, and Mr. Daily report no relevant disclosures. 
 

A version of this article appeared on Medscape.com.

BOSTON — Patients with acute colonic diverticulitis are more likely to be seen by primary care providers than by emergency physicians, representing a shift in the way clinicians detect and treat the condition.

Acute colonic diverticulitis affects roughly 180 per 100,000 people per year in the United States.

CT of the abdomen and pelvis may not be a first-line method to detect diverticulitis in the primary care setting as it has been in emergent care, according to Kaveh Sharzehi, MD, MS, associate professor of medicine in the Division of Gastroenterology and Hepatology at Oregon Health & Science University in Portland.

Indeed, clinical guidelines by multiple physician groups recommend that providers use a more individualized approach to detecting and treating the condition. 

“There is still great value in proper and thorough physical history and some adjunct testing,” Dr. Sharzehi told attendees during a presentation on April 20 at the American College of Physicians Internal Medicine Meeting 2024. These two methods can detect the disease up to 65% of the time, Dr. Sharzehi added.

An initial evaluation of a patient with suspected acute diverticulitis should first assess the patient’s history of abdominal pain, fever, and leukocytosis, Dr. Sharzehi said. 

A C-reactive protein level > 50 mg/L “almost doubles the odds of having diverticulitis,” Dr. Sharzehi said. Studies also suggest increased levels of procalcitonin and fecal calprotectin can indicate the presence of the condition.

The American Gastroenterological Association (AGA) and the American College of Physicians recommend abdominal CT if clinicians are uncertain of the diagnosis, and to evaluate potential complications in severe cases. Ultrasound and MRI can be useful alternatives, according to guidelines from the American Society of Colon and Rectal Surgeons.

The chances of developing diverticulitis increase with age. More than 60% of Americans aged 60 years or older have diverticulosis, a condition characterized by small pouches in the colon lining that can weaken the colon wall. Less than 5% of people with diverticulosis go on to develop diverticulitis. 

“Aspirin and opioid use are also risk factors, likely from their effect on the colonic transit time and causing constipation that might contribute to diverticulitis, but that›s not very well understood,” Dr. Sharzehi said. 

Medical management has shifted from predominantly inpatient to predominantly outpatient care, Dr. Sharzehi told attendees 

“Unfortunately, there are not that many supportive guidelines for what diet a patient should have in the acute setting of diverticulitis,” he said. 

Patients with a mild case may benefit from a clear liquid diet; for some patients, high-fiber diets, regular physical activity, and statins may protect against recurrence. 

Current guidelines recommend against prescribing antibiotics for most cases because evidence suggests that diverticulitis is primarily an inflammatory process that can result in small tears in the diverticulum, rather than the disease being a complication of existing tears. 

Patients should also not be treated with probiotics or 5-aminosalicylic acid agents, Dr. Sharzehi said.

“My practice is in the Pacific Northwest, where there’s a lot of belief in naturopathic remedies, so we get a lot of questions about supplements and probiotics in preventing diverticulitis,” he said. “We don’t think it does help, and this is unanimous among all the main [physician] societies.” 

The AGA recommends referring patients for a colonoscopy within a year after diverticulitis symptoms have resided. 

Severe or unresolved cases could require inpatient procedures such as percutaneous drainage or surgery. An estimated 15%-30% of patients admitted to hospital with acute diverticulitis require surgery, Dr. Sharzehi said. 

Surgery may become an option for patients who have recurrent cases of the disease, even if not severe, Dr. Sharzehi said.

Dr. Sharzehi reported no relevant disclosures.
 

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

BOSTON — Patients with acute colonic diverticulitis are more likely to be seen by primary care providers than by emergency physicians, representing a shift in the way clinicians detect and treat the condition.

Acute colonic diverticulitis affects roughly 180 per 100,000 people per year in the United States.

CT of the abdomen and pelvis may not be a first-line method to detect diverticulitis in the primary care setting as it has been in emergent care, according to Kaveh Sharzehi, MD, MS, associate professor of medicine in the Division of Gastroenterology and Hepatology at Oregon Health & Science University in Portland.

Indeed, clinical guidelines by multiple physician groups recommend that providers use a more individualized approach to detecting and treating the condition. 

“There is still great value in proper and thorough physical history and some adjunct testing,” Dr. Sharzehi told attendees during a presentation on April 20 at the American College of Physicians Internal Medicine Meeting 2024. These two methods can detect the disease up to 65% of the time, Dr. Sharzehi added.

An initial evaluation of a patient with suspected acute diverticulitis should first assess the patient’s history of abdominal pain, fever, and leukocytosis, Dr. Sharzehi said. 

A C-reactive protein level > 50 mg/L “almost doubles the odds of having diverticulitis,” Dr. Sharzehi said. Studies also suggest increased levels of procalcitonin and fecal calprotectin can indicate the presence of the condition.

The American Gastroenterological Association (AGA) and the American College of Physicians recommend abdominal CT if clinicians are uncertain of the diagnosis, and to evaluate potential complications in severe cases. Ultrasound and MRI can be useful alternatives, according to guidelines from the American Society of Colon and Rectal Surgeons.

The chances of developing diverticulitis increase with age. More than 60% of Americans aged 60 years or older have diverticulosis, a condition characterized by small pouches in the colon lining that can weaken the colon wall. Less than 5% of people with diverticulosis go on to develop diverticulitis. 

“Aspirin and opioid use are also risk factors, likely from their effect on the colonic transit time and causing constipation that might contribute to diverticulitis, but that›s not very well understood,” Dr. Sharzehi said. 

Medical management has shifted from predominantly inpatient to predominantly outpatient care, Dr. Sharzehi told attendees 

“Unfortunately, there are not that many supportive guidelines for what diet a patient should have in the acute setting of diverticulitis,” he said. 

Patients with a mild case may benefit from a clear liquid diet; for some patients, high-fiber diets, regular physical activity, and statins may protect against recurrence. 

Current guidelines recommend against prescribing antibiotics for most cases because evidence suggests that diverticulitis is primarily an inflammatory process that can result in small tears in the diverticulum, rather than the disease being a complication of existing tears. 

Patients should also not be treated with probiotics or 5-aminosalicylic acid agents, Dr. Sharzehi said.

“My practice is in the Pacific Northwest, where there’s a lot of belief in naturopathic remedies, so we get a lot of questions about supplements and probiotics in preventing diverticulitis,” he said. “We don’t think it does help, and this is unanimous among all the main [physician] societies.” 

The AGA recommends referring patients for a colonoscopy within a year after diverticulitis symptoms have resided. 

Severe or unresolved cases could require inpatient procedures such as percutaneous drainage or surgery. An estimated 15%-30% of patients admitted to hospital with acute diverticulitis require surgery, Dr. Sharzehi said. 

Surgery may become an option for patients who have recurrent cases of the disease, even if not severe, Dr. Sharzehi said.

Dr. Sharzehi reported no relevant disclosures.
 

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

BOSTON — Patients with acute colonic diverticulitis are more likely to be seen by primary care providers than by emergency physicians, representing a shift in the way clinicians detect and treat the condition.

Acute colonic diverticulitis affects roughly 180 per 100,000 people per year in the United States.

CT of the abdomen and pelvis may not be a first-line method to detect diverticulitis in the primary care setting as it has been in emergent care, according to Kaveh Sharzehi, MD, MS, associate professor of medicine in the Division of Gastroenterology and Hepatology at Oregon Health & Science University in Portland.

Indeed, clinical guidelines by multiple physician groups recommend that providers use a more individualized approach to detecting and treating the condition. 

“There is still great value in proper and thorough physical history and some adjunct testing,” Dr. Sharzehi told attendees during a presentation on April 20 at the American College of Physicians Internal Medicine Meeting 2024. These two methods can detect the disease up to 65% of the time, Dr. Sharzehi added.

An initial evaluation of a patient with suspected acute diverticulitis should first assess the patient’s history of abdominal pain, fever, and leukocytosis, Dr. Sharzehi said. 

A C-reactive protein level > 50 mg/L “almost doubles the odds of having diverticulitis,” Dr. Sharzehi said. Studies also suggest increased levels of procalcitonin and fecal calprotectin can indicate the presence of the condition.

The American Gastroenterological Association (AGA) and the American College of Physicians recommend abdominal CT if clinicians are uncertain of the diagnosis, and to evaluate potential complications in severe cases. Ultrasound and MRI can be useful alternatives, according to guidelines from the American Society of Colon and Rectal Surgeons.

The chances of developing diverticulitis increase with age. More than 60% of Americans aged 60 years or older have diverticulosis, a condition characterized by small pouches in the colon lining that can weaken the colon wall. Less than 5% of people with diverticulosis go on to develop diverticulitis. 

“Aspirin and opioid use are also risk factors, likely from their effect on the colonic transit time and causing constipation that might contribute to diverticulitis, but that›s not very well understood,” Dr. Sharzehi said. 

Medical management has shifted from predominantly inpatient to predominantly outpatient care, Dr. Sharzehi told attendees 

“Unfortunately, there are not that many supportive guidelines for what diet a patient should have in the acute setting of diverticulitis,” he said. 

Patients with a mild case may benefit from a clear liquid diet; for some patients, high-fiber diets, regular physical activity, and statins may protect against recurrence. 

Current guidelines recommend against prescribing antibiotics for most cases because evidence suggests that diverticulitis is primarily an inflammatory process that can result in small tears in the diverticulum, rather than the disease being a complication of existing tears. 

Patients should also not be treated with probiotics or 5-aminosalicylic acid agents, Dr. Sharzehi said.

“My practice is in the Pacific Northwest, where there’s a lot of belief in naturopathic remedies, so we get a lot of questions about supplements and probiotics in preventing diverticulitis,” he said. “We don’t think it does help, and this is unanimous among all the main [physician] societies.” 

The AGA recommends referring patients for a colonoscopy within a year after diverticulitis symptoms have resided. 

Severe or unresolved cases could require inpatient procedures such as percutaneous drainage or surgery. An estimated 15%-30% of patients admitted to hospital with acute diverticulitis require surgery, Dr. Sharzehi said. 

Surgery may become an option for patients who have recurrent cases of the disease, even if not severe, Dr. Sharzehi said.

Dr. Sharzehi reported no relevant disclosures.
 

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

The utility of cannabinoids to treat most medical conditions remains uncertain at best, but for at least three indications the data lean in favor of effectiveness, Ellie Grossman, MD, MPH, told attendees recently at the 2024 American College of Physicians Internal Medicine meeting.

Those are neuropathic pain, chemotherapy-induced nausea or vomiting, and spasticity in people with multiple sclerosis, said Dr. Grossman, an instructor at Harvard Medical School in Boston and medical director for primary care/behavioral health integration at Cambridge Health Alliance in Somerville, Massachusetts.

Dearth of Research Persists

Research is sorely lacking and of low quality in the field for many reasons, Dr. Grossman said. Most of the products tested come from outside the United States and often are synthetic and taken orally — which does not match the real-world use when patients go to dispensaries for cannabis derived directly from plants (or the plant product itself). And studies often rely on self-report.

Chronic pain is by far the top reason patients say they use medical cannabis, Dr. Grossman said. A Cochrane review of 16 studies found only that the potential benefits of cannabis may outweigh the potential harms for chronic neuropathic pain.
 

No Evidence in OUD

Dr. Grossman said she is frequently asked if cannabis can help people quit taking opioids. The answer seems to be no. A study published earlier this year in states with legalized medical or recreational cannabis found no difference between rates of opioid overdose compared with states with no such laws. “It seems like it doesn’t do anything to help us with our opioid problem,” she said.

Nor does high-quality evidence exist showing use of cannabis can improve sleep, she said. A 2022 systematic review found fewer than half of studies showed the substance useful for sleep outcomes. “Where studies were positives, it was in people who had chronic pain,” Dr. Grossman noted. Research indicates cannabis may have substantial benefit for chronic pain compared with placebo.
 

Potential Harms

If the medical benefits of cannabis are murky, the evidence for its potential harms, at least in the short term, are clearer, according to Dr. Grossman. A simplified guideline for prescribing medical cannabinoids in primary care includes sedation, feeling high, dizziness, speech disorders, muscle twitching, hypotension, and several other conditions among the potential hazards of the drug. 

But the potential for long-term harm is uncertain. “All the evidence comes from people who have been using it for recreational reasons,” where there may be co-use of tobacco, self-reported outcomes, and recall bias, she said. The characteristics of people using cannabis recreationally often differ from those using it medicinally.
 

Use With Other Controlled Substances

Dr. Grossman said clinicians should consider whether the co-use of cannabis and other controlled substances, such as benzodiazepines, opioids, or Adderall, raises the potential risks associated with those drugs. “Ultimately it comes down to talking to your patients,” she said. If a toxicity screen shows the presence of controlled substances, ask about their experience with the drugs they are using and let them know your main concern is their safety.

Dr. Grossman reported no relevant financial conflicts of interest.

A version of this article appeared on Medscape.com.

The utility of cannabinoids to treat most medical conditions remains uncertain at best, but for at least three indications the data lean in favor of effectiveness, Ellie Grossman, MD, MPH, told attendees recently at the 2024 American College of Physicians Internal Medicine meeting.

Those are neuropathic pain, chemotherapy-induced nausea or vomiting, and spasticity in people with multiple sclerosis, said Dr. Grossman, an instructor at Harvard Medical School in Boston and medical director for primary care/behavioral health integration at Cambridge Health Alliance in Somerville, Massachusetts.

Dearth of Research Persists

Research is sorely lacking and of low quality in the field for many reasons, Dr. Grossman said. Most of the products tested come from outside the United States and often are synthetic and taken orally — which does not match the real-world use when patients go to dispensaries for cannabis derived directly from plants (or the plant product itself). And studies often rely on self-report.

Chronic pain is by far the top reason patients say they use medical cannabis, Dr. Grossman said. A Cochrane review of 16 studies found only that the potential benefits of cannabis may outweigh the potential harms for chronic neuropathic pain.
 

No Evidence in OUD

Dr. Grossman said she is frequently asked if cannabis can help people quit taking opioids. The answer seems to be no. A study published earlier this year in states with legalized medical or recreational cannabis found no difference between rates of opioid overdose compared with states with no such laws. “It seems like it doesn’t do anything to help us with our opioid problem,” she said.

Nor does high-quality evidence exist showing use of cannabis can improve sleep, she said. A 2022 systematic review found fewer than half of studies showed the substance useful for sleep outcomes. “Where studies were positives, it was in people who had chronic pain,” Dr. Grossman noted. Research indicates cannabis may have substantial benefit for chronic pain compared with placebo.
 

Potential Harms

If the medical benefits of cannabis are murky, the evidence for its potential harms, at least in the short term, are clearer, according to Dr. Grossman. A simplified guideline for prescribing medical cannabinoids in primary care includes sedation, feeling high, dizziness, speech disorders, muscle twitching, hypotension, and several other conditions among the potential hazards of the drug. 

But the potential for long-term harm is uncertain. “All the evidence comes from people who have been using it for recreational reasons,” where there may be co-use of tobacco, self-reported outcomes, and recall bias, she said. The characteristics of people using cannabis recreationally often differ from those using it medicinally.
 

Use With Other Controlled Substances

Dr. Grossman said clinicians should consider whether the co-use of cannabis and other controlled substances, such as benzodiazepines, opioids, or Adderall, raises the potential risks associated with those drugs. “Ultimately it comes down to talking to your patients,” she said. If a toxicity screen shows the presence of controlled substances, ask about their experience with the drugs they are using and let them know your main concern is their safety.

Dr. Grossman reported no relevant financial conflicts of interest.

A version of this article appeared on Medscape.com.

The utility of cannabinoids to treat most medical conditions remains uncertain at best, but for at least three indications the data lean in favor of effectiveness, Ellie Grossman, MD, MPH, told attendees recently at the 2024 American College of Physicians Internal Medicine meeting.

Those are neuropathic pain, chemotherapy-induced nausea or vomiting, and spasticity in people with multiple sclerosis, said Dr. Grossman, an instructor at Harvard Medical School in Boston and medical director for primary care/behavioral health integration at Cambridge Health Alliance in Somerville, Massachusetts.

Dearth of Research Persists

Research is sorely lacking and of low quality in the field for many reasons, Dr. Grossman said. Most of the products tested come from outside the United States and often are synthetic and taken orally — which does not match the real-world use when patients go to dispensaries for cannabis derived directly from plants (or the plant product itself). And studies often rely on self-report.

Chronic pain is by far the top reason patients say they use medical cannabis, Dr. Grossman said. A Cochrane review of 16 studies found only that the potential benefits of cannabis may outweigh the potential harms for chronic neuropathic pain.
 

No Evidence in OUD

Dr. Grossman said she is frequently asked if cannabis can help people quit taking opioids. The answer seems to be no. A study published earlier this year in states with legalized medical or recreational cannabis found no difference between rates of opioid overdose compared with states with no such laws. “It seems like it doesn’t do anything to help us with our opioid problem,” she said.

Nor does high-quality evidence exist showing use of cannabis can improve sleep, she said. A 2022 systematic review found fewer than half of studies showed the substance useful for sleep outcomes. “Where studies were positives, it was in people who had chronic pain,” Dr. Grossman noted. Research indicates cannabis may have substantial benefit for chronic pain compared with placebo.
 

Potential Harms

If the medical benefits of cannabis are murky, the evidence for its potential harms, at least in the short term, are clearer, according to Dr. Grossman. A simplified guideline for prescribing medical cannabinoids in primary care includes sedation, feeling high, dizziness, speech disorders, muscle twitching, hypotension, and several other conditions among the potential hazards of the drug. 

But the potential for long-term harm is uncertain. “All the evidence comes from people who have been using it for recreational reasons,” where there may be co-use of tobacco, self-reported outcomes, and recall bias, she said. The characteristics of people using cannabis recreationally often differ from those using it medicinally.
 

Use With Other Controlled Substances

Dr. Grossman said clinicians should consider whether the co-use of cannabis and other controlled substances, such as benzodiazepines, opioids, or Adderall, raises the potential risks associated with those drugs. “Ultimately it comes down to talking to your patients,” she said. If a toxicity screen shows the presence of controlled substances, ask about their experience with the drugs they are using and let them know your main concern is their safety.

Dr. Grossman reported no relevant financial conflicts of interest.

A version of this article appeared on Medscape.com.

VIENNA — The glucagon-like peptide 1 (GLP-1) receptor agonist semaglutide (Wegovy) not only induced weight loss but also improved knee pain in people with knee osteoarthritis (OA) and obesity, according to results from the STEP 9 study reported at the Osteoarthritis Research Society International (OARSI) 2024  World Congress.

From baseline to week 68, the mean change in knee pain assessed using the Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain score was a reduction of 41.7 points for semaglutide and a decrease of 27.5 points for a matching placebo. The estimated treatment difference of 14.1 points between the groups was statistically significant (P < .001).

As for weight loss, this also fell by a significantly greater amount in the people treated with semaglutide vs those given placebo, with respective reductions of 13.7% and 3.2% from baseline, with an estimated 10.5% greater weight loss with semaglutide.

Sara Freeman/Medscape Medical News

“The interesting thing is whether there’s a specific action of GLP-1 receptor agonists on the joint, not through the weight loss but by itself,” principal study investigator Henning Bliddal, MD, DMSc, told this news organization ahead of reporting the results at OARSI 2024.

Weight loss is “obviously good” because “the knees suffer from the weight. But whether it’s good for the knee or just for the health or the well-being of the person is another matter,” said Dr. Bliddal, who is director of the Parker Institute at Bispebjerg Frederiksberg Hospital in Copenhagen, Denmark.
 

Not Approved in OA

Semaglutide and other potentially weight loss-inducing drugs are not currently indicated for use specifically in OA, Tonia Vincent, MBBS, PhD, told this news organization, and so “I think we have to be very cautious,” she said.

“Weight loss is one of the few things that has been shown to be successful in clinical trials,” said Dr. Vincent, who is a professor of musculoskeletal biology and an honorary rheumatologist at the Kennedy Institute of Rheumatology at Oxford University in Oxford, England.

“People always feel better too when they lose weight, so that helps manage pain. So, I’d be very surprised if there isn’t a benefit,” she added.

“I just think we need to know more about the long-term use of these drugs, whether the healthcare system can afford them, and how we would ration them.”
 

Previous Work

The STEP 9 study is not the first time that Dr. Bliddal has investigated the effects of a GLP-1 receptor agonist in people with knee OA, but it is the first to have shown a significant effect on knee pain.

Previously, results from the LOSEIT trial with liraglutide demonstrated that, after an 8-week dietary intervention run-in phase, people who were treated with the GLP-1 receptor agonist lost an average of 2.8 kg in body weight over a period of 1 year, vs a 1.2 kg gain in the placebo group. Knee injury and Osteoarthritis Outcome Scores, however, were largely unaffected.

“The study was more or less negative for knee pain because at that time we had to pretreat patients with some kind of weight loss before they were allowed to have the liraglutide,” Dr. Bliddal said.

“There’s so many different considerations with diets and the different ways that [dietary modification] is performed, that could be part of the explanation why some people didn’t find the pain relief,” Dr. Bliddal suggested.
 

STEP 9 Study Design

No pre-study dietary intervention was required in the STEP 9 trial, although a reduced-calorie diet and increased physical exercise were used alongside both semaglutide and placebo treatment.

STEP 9 was a multicenter, multinational phase 3 clinical trial that enrolled people if they had a body mass index (BMI) of > 30, had a clinical diagnosis of knee OA with moderate radiographic changes (Kellgren-Lawrence grade of 2-3), and were experiencing knee pain.

In addition to a baseline WOMAC pain score of at least 40 points (where 0 represents no and 100 the worst pain), the participants had to have a WOMAC numerical rating scale (NRS) score of ≥ 3.1.

A total of 407 participants were recruited and randomly allocated, 2:1, to receive once-weekly subcutaneous injections of either semaglutide 2.4 mg or placebo for a total of 68 weeks.

Dr. Bliddal presented demographic information only for the study population as a whole, showing that the mean was 56 years, 81.6% were women, 60.9% were White, 11.8% Native American, 7.6% Black, and 19.7% of other ethnic origin.

Moreover, the mean bodyweight at baseline was 108.6 kg, and the mean baseline BMI was 40.3, with 75% of participants having a BMI ≥ 35. The mean waist circumference was 118.7 cm. The mean baseline WOMAC pain score was 70.9.
 

Other Findings

In addition to the reductions seen in the coprimary endpoints of weight loss and knee pain, the WOMAC physical function score was also reduced from baseline to week 68 to a greater degree in the semaglutide than placebo arm, by a respective 41.5 vs 26.7 points, with a significant estimated treatment difference of -14.9 points.

“The use of pain medication went down as well; you can see the drop was faster in the semaglutide group than the placebo group, and it was maintained throughout the study,” Dr. Bliddal said during his presentation. He noted that patients had to temporarily stop taking pain relievers such as acetaminophen 3 days before their pain was assessed.

Additional findings reported in the abstract, but not presented at the meeting, were a significant estimated treatment difference of -1.0 in NRS pain intensity, more people treated with semaglutide than placebo achieving ≥ 5% (87.0% vs 29.2%) or ≥ 10% (70.4% vs 9.2%) weight loss.

“Safety and tolerability with semaglutide were consistent with the global STEP program and the GLP-1 receptor agonist class in general,” Dr. Bliddal reported.

Serious adverse events occurred in a respective 10.0% and 8.1% of participants, and adverse events leading to discontinuation were recorded in 6.7% and 3%. Around one third (2.2%) of those leading to discontinuation in the semaglutide arm were gastrointestinal adverse events.

The STEP 9 study was funded by Novo Nordisk. Henning is a principal investigator for the trial and acknowledged that research grants were received from Novo Nordisk to his institution, as well as consulting fees and honoraria. He has also received congress and travel support from Contura. Dr. Vincent was not involved in the study and had no relevant conflicts of interest to disclose.

A version of this article appeared on Medscape.com.

VIENNA — The glucagon-like peptide 1 (GLP-1) receptor agonist semaglutide (Wegovy) not only induced weight loss but also improved knee pain in people with knee osteoarthritis (OA) and obesity, according to results from the STEP 9 study reported at the Osteoarthritis Research Society International (OARSI) 2024  World Congress.

From baseline to week 68, the mean change in knee pain assessed using the Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain score was a reduction of 41.7 points for semaglutide and a decrease of 27.5 points for a matching placebo. The estimated treatment difference of 14.1 points between the groups was statistically significant (P < .001).

As for weight loss, this also fell by a significantly greater amount in the people treated with semaglutide vs those given placebo, with respective reductions of 13.7% and 3.2% from baseline, with an estimated 10.5% greater weight loss with semaglutide.

Sara Freeman/Medscape Medical News

“The interesting thing is whether there’s a specific action of GLP-1 receptor agonists on the joint, not through the weight loss but by itself,” principal study investigator Henning Bliddal, MD, DMSc, told this news organization ahead of reporting the results at OARSI 2024.

Weight loss is “obviously good” because “the knees suffer from the weight. But whether it’s good for the knee or just for the health or the well-being of the person is another matter,” said Dr. Bliddal, who is director of the Parker Institute at Bispebjerg Frederiksberg Hospital in Copenhagen, Denmark.
 

Not Approved in OA

Semaglutide and other potentially weight loss-inducing drugs are not currently indicated for use specifically in OA, Tonia Vincent, MBBS, PhD, told this news organization, and so “I think we have to be very cautious,” she said.

“Weight loss is one of the few things that has been shown to be successful in clinical trials,” said Dr. Vincent, who is a professor of musculoskeletal biology and an honorary rheumatologist at the Kennedy Institute of Rheumatology at Oxford University in Oxford, England.

“People always feel better too when they lose weight, so that helps manage pain. So, I’d be very surprised if there isn’t a benefit,” she added.

“I just think we need to know more about the long-term use of these drugs, whether the healthcare system can afford them, and how we would ration them.”
 

Previous Work

The STEP 9 study is not the first time that Dr. Bliddal has investigated the effects of a GLP-1 receptor agonist in people with knee OA, but it is the first to have shown a significant effect on knee pain.

Previously, results from the LOSEIT trial with liraglutide demonstrated that, after an 8-week dietary intervention run-in phase, people who were treated with the GLP-1 receptor agonist lost an average of 2.8 kg in body weight over a period of 1 year, vs a 1.2 kg gain in the placebo group. Knee injury and Osteoarthritis Outcome Scores, however, were largely unaffected.

“The study was more or less negative for knee pain because at that time we had to pretreat patients with some kind of weight loss before they were allowed to have the liraglutide,” Dr. Bliddal said.

“There’s so many different considerations with diets and the different ways that [dietary modification] is performed, that could be part of the explanation why some people didn’t find the pain relief,” Dr. Bliddal suggested.
 

STEP 9 Study Design

No pre-study dietary intervention was required in the STEP 9 trial, although a reduced-calorie diet and increased physical exercise were used alongside both semaglutide and placebo treatment.

STEP 9 was a multicenter, multinational phase 3 clinical trial that enrolled people if they had a body mass index (BMI) of > 30, had a clinical diagnosis of knee OA with moderate radiographic changes (Kellgren-Lawrence grade of 2-3), and were experiencing knee pain.

In addition to a baseline WOMAC pain score of at least 40 points (where 0 represents no and 100 the worst pain), the participants had to have a WOMAC numerical rating scale (NRS) score of ≥ 3.1.

A total of 407 participants were recruited and randomly allocated, 2:1, to receive once-weekly subcutaneous injections of either semaglutide 2.4 mg or placebo for a total of 68 weeks.

Dr. Bliddal presented demographic information only for the study population as a whole, showing that the mean was 56 years, 81.6% were women, 60.9% were White, 11.8% Native American, 7.6% Black, and 19.7% of other ethnic origin.

Moreover, the mean bodyweight at baseline was 108.6 kg, and the mean baseline BMI was 40.3, with 75% of participants having a BMI ≥ 35. The mean waist circumference was 118.7 cm. The mean baseline WOMAC pain score was 70.9.
 

Other Findings

In addition to the reductions seen in the coprimary endpoints of weight loss and knee pain, the WOMAC physical function score was also reduced from baseline to week 68 to a greater degree in the semaglutide than placebo arm, by a respective 41.5 vs 26.7 points, with a significant estimated treatment difference of -14.9 points.

“The use of pain medication went down as well; you can see the drop was faster in the semaglutide group than the placebo group, and it was maintained throughout the study,” Dr. Bliddal said during his presentation. He noted that patients had to temporarily stop taking pain relievers such as acetaminophen 3 days before their pain was assessed.

Additional findings reported in the abstract, but not presented at the meeting, were a significant estimated treatment difference of -1.0 in NRS pain intensity, more people treated with semaglutide than placebo achieving ≥ 5% (87.0% vs 29.2%) or ≥ 10% (70.4% vs 9.2%) weight loss.

“Safety and tolerability with semaglutide were consistent with the global STEP program and the GLP-1 receptor agonist class in general,” Dr. Bliddal reported.

Serious adverse events occurred in a respective 10.0% and 8.1% of participants, and adverse events leading to discontinuation were recorded in 6.7% and 3%. Around one third (2.2%) of those leading to discontinuation in the semaglutide arm were gastrointestinal adverse events.

The STEP 9 study was funded by Novo Nordisk. Henning is a principal investigator for the trial and acknowledged that research grants were received from Novo Nordisk to his institution, as well as consulting fees and honoraria. He has also received congress and travel support from Contura. Dr. Vincent was not involved in the study and had no relevant conflicts of interest to disclose.

A version of this article appeared on Medscape.com.

VIENNA — The glucagon-like peptide 1 (GLP-1) receptor agonist semaglutide (Wegovy) not only induced weight loss but also improved knee pain in people with knee osteoarthritis (OA) and obesity, according to results from the STEP 9 study reported at the Osteoarthritis Research Society International (OARSI) 2024  World Congress.

From baseline to week 68, the mean change in knee pain assessed using the Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain score was a reduction of 41.7 points for semaglutide and a decrease of 27.5 points for a matching placebo. The estimated treatment difference of 14.1 points between the groups was statistically significant (P < .001).

As for weight loss, this also fell by a significantly greater amount in the people treated with semaglutide vs those given placebo, with respective reductions of 13.7% and 3.2% from baseline, with an estimated 10.5% greater weight loss with semaglutide.

Sara Freeman/Medscape Medical News

“The interesting thing is whether there’s a specific action of GLP-1 receptor agonists on the joint, not through the weight loss but by itself,” principal study investigator Henning Bliddal, MD, DMSc, told this news organization ahead of reporting the results at OARSI 2024.

Weight loss is “obviously good” because “the knees suffer from the weight. But whether it’s good for the knee or just for the health or the well-being of the person is another matter,” said Dr. Bliddal, who is director of the Parker Institute at Bispebjerg Frederiksberg Hospital in Copenhagen, Denmark.
 

Not Approved in OA

Semaglutide and other potentially weight loss-inducing drugs are not currently indicated for use specifically in OA, Tonia Vincent, MBBS, PhD, told this news organization, and so “I think we have to be very cautious,” she said.

“Weight loss is one of the few things that has been shown to be successful in clinical trials,” said Dr. Vincent, who is a professor of musculoskeletal biology and an honorary rheumatologist at the Kennedy Institute of Rheumatology at Oxford University in Oxford, England.

“People always feel better too when they lose weight, so that helps manage pain. So, I’d be very surprised if there isn’t a benefit,” she added.

“I just think we need to know more about the long-term use of these drugs, whether the healthcare system can afford them, and how we would ration them.”
 

Previous Work

The STEP 9 study is not the first time that Dr. Bliddal has investigated the effects of a GLP-1 receptor agonist in people with knee OA, but it is the first to have shown a significant effect on knee pain.

Previously, results from the LOSEIT trial with liraglutide demonstrated that, after an 8-week dietary intervention run-in phase, people who were treated with the GLP-1 receptor agonist lost an average of 2.8 kg in body weight over a period of 1 year, vs a 1.2 kg gain in the placebo group. Knee injury and Osteoarthritis Outcome Scores, however, were largely unaffected.

“The study was more or less negative for knee pain because at that time we had to pretreat patients with some kind of weight loss before they were allowed to have the liraglutide,” Dr. Bliddal said.

“There’s so many different considerations with diets and the different ways that [dietary modification] is performed, that could be part of the explanation why some people didn’t find the pain relief,” Dr. Bliddal suggested.
 

STEP 9 Study Design

No pre-study dietary intervention was required in the STEP 9 trial, although a reduced-calorie diet and increased physical exercise were used alongside both semaglutide and placebo treatment.

STEP 9 was a multicenter, multinational phase 3 clinical trial that enrolled people if they had a body mass index (BMI) of > 30, had a clinical diagnosis of knee OA with moderate radiographic changes (Kellgren-Lawrence grade of 2-3), and were experiencing knee pain.

In addition to a baseline WOMAC pain score of at least 40 points (where 0 represents no and 100 the worst pain), the participants had to have a WOMAC numerical rating scale (NRS) score of ≥ 3.1.

A total of 407 participants were recruited and randomly allocated, 2:1, to receive once-weekly subcutaneous injections of either semaglutide 2.4 mg or placebo for a total of 68 weeks.

Dr. Bliddal presented demographic information only for the study population as a whole, showing that the mean was 56 years, 81.6% were women, 60.9% were White, 11.8% Native American, 7.6% Black, and 19.7% of other ethnic origin.

Moreover, the mean bodyweight at baseline was 108.6 kg, and the mean baseline BMI was 40.3, with 75% of participants having a BMI ≥ 35. The mean waist circumference was 118.7 cm. The mean baseline WOMAC pain score was 70.9.
 

Other Findings

In addition to the reductions seen in the coprimary endpoints of weight loss and knee pain, the WOMAC physical function score was also reduced from baseline to week 68 to a greater degree in the semaglutide than placebo arm, by a respective 41.5 vs 26.7 points, with a significant estimated treatment difference of -14.9 points.

“The use of pain medication went down as well; you can see the drop was faster in the semaglutide group than the placebo group, and it was maintained throughout the study,” Dr. Bliddal said during his presentation. He noted that patients had to temporarily stop taking pain relievers such as acetaminophen 3 days before their pain was assessed.

Additional findings reported in the abstract, but not presented at the meeting, were a significant estimated treatment difference of -1.0 in NRS pain intensity, more people treated with semaglutide than placebo achieving ≥ 5% (87.0% vs 29.2%) or ≥ 10% (70.4% vs 9.2%) weight loss.

“Safety and tolerability with semaglutide were consistent with the global STEP program and the GLP-1 receptor agonist class in general,” Dr. Bliddal reported.

Serious adverse events occurred in a respective 10.0% and 8.1% of participants, and adverse events leading to discontinuation were recorded in 6.7% and 3%. Around one third (2.2%) of those leading to discontinuation in the semaglutide arm were gastrointestinal adverse events.

The STEP 9 study was funded by Novo Nordisk. Henning is a principal investigator for the trial and acknowledged that research grants were received from Novo Nordisk to his institution, as well as consulting fees and honoraria. He has also received congress and travel support from Contura. Dr. Vincent was not involved in the study and had no relevant conflicts of interest to disclose.

A version of this article appeared on Medscape.com.

DENVER — Lidocaine injections into the greater occipital nerve relieve severe, refractory migraine attacks in children, results of a randomized controlled trial show. 

Investigators found children receiving bilateral occipital nerve blocks with 2% lidocaine had significantly greater pain relief than that of peers receiving saline injections. 

Cases series have shown a benefit of peripheral nerve blocks (PNBs) — injections of local anesthetics over branches of the occipital or trigeminal nerve — for severe, refractory headache in children.  

Although 80% of pediatric headache specialists use PNBs, there is “inconsistent insurance coverage” for this treatment, which had not been tested in a randomized controlled trial in children before now, lead investigator Christina Szperka, MD, with the Pediatric Headache Program, Department of Neurology, University of Pennsylvania Perelman School of Medicine, Philadelphia, told delegates attending the 2024 annual meeting of the American Academy of Neurology. 
 

Significant Results

Investigators enrolled 58 children and adolescents with acute status migrainosus. The mean age was 16 years, and reported gender was female for 44 participants, male for 11 participants, and nonbinary or transgender in 3 participants. Participants had a migraine flare duration of 22 days and had not responded to other treatments. 

All participants had topical lidocaine cream applied for 30 minutes as a run-in step and could decline injections if they experienced sufficient benefit from cream alone. 

“We used a lidocaine cream lead-in for two reasons. One was to try to see if we could address the issue of high placebo response in pediatric trials in particular, and also to see if we could help with blinding to injection,” said Dr. Szperka. 

Topical lidocaine cream led to a small decrease in pain score overall (0.2 point on a 0-10 scale), and all participants proceeded to randomized blinded bilateral greater occipital nerve injection with 2% lidocaine or saline, she reported. 

On the primary endpoint — change in pain score at 30 minutes — lidocaine was significantly more effective than saline, achieving a 2.3-point decrease on average (on a 0-10 scale) vs a 1.1-point decrease with saline (P = .01).

A 2-point pain reduction was achieved in 69% of patients in the lidocaine group versus 34% in the saline group.

Three quarters (76%) of patients getting lidocaine reported at least partial relief in severity or location of pain compared with 48% of those getting saline (P = .03). Rates of pain freedom at 30 minutes were 17% and 7%, respectively, and at 24 hours were 14% and 0%, respectively.

The majority of adverse events were mild and fairly equal across groups and included anxiety, worsening headache, injection site pain, dizziness, and numbness (more so with lidocaine). There was one case of anaphylaxis after lidocaine injection.

Quite unexpectedly, said Dr. Szperka, patients rated the saline injection as more painful than the lidocaine injection. “This was not what I expected going in, and I think is relevant for future trials,” she said.
 

Encouraging Results 

Reached for comment, Shaheen Lakhan, MD, a neurologist and researcher based in Miami, said that as a neurologist and pain physician, he sees firsthand the “devastating impact of status migrainosus on children.”

“These debilitating headaches can rob them of precious school days, hindering learning and social interaction,” said Dr. Lakhan. “The constant pain and fear of the next attack can also take a toll on their emotional well-being.”

The impact on families is significant as well, highlighting the need to find more effective treatments, Dr. Lakhan said. 

“Traditionally, we’ve relied on case studies to see the benefits of nerve blocks for migraine in younger patients. This is the first randomized controlled trial that shows lidocaine injections can be significantly more effective than a placebo for these unrelenting migraines,” he said.

“It’s important to note that this is a relatively small study, and not without safety concerns, including rare but potentially life-threatening anaphylaxis to lidocaine,” Dr. Lakhan added. “More research is needed, but these findings are encouraging. Lidocaine injections could become a valuable tool for managing treatment-resistant migraines in adolescents and young adults.”

The study was supported by a grant from the National Institute of Neurological Disorders and Stroke. Dr. Szperka is a consultant for AbbVie and Teva; serves on a Data Safety Monitoring Board for Eli Lilly and Upsher-Smith; and is a site principal investigator for AbbVie, Amgen, Biohaven/Pfizer, Teva, and Theranica. Dr. Lakhan had no disclosures.
 

A version of this article appeared on Medscape.com.

DENVER — Lidocaine injections into the greater occipital nerve relieve severe, refractory migraine attacks in children, results of a randomized controlled trial show. 

Investigators found children receiving bilateral occipital nerve blocks with 2% lidocaine had significantly greater pain relief than that of peers receiving saline injections. 

Cases series have shown a benefit of peripheral nerve blocks (PNBs) — injections of local anesthetics over branches of the occipital or trigeminal nerve — for severe, refractory headache in children.  

Although 80% of pediatric headache specialists use PNBs, there is “inconsistent insurance coverage” for this treatment, which had not been tested in a randomized controlled trial in children before now, lead investigator Christina Szperka, MD, with the Pediatric Headache Program, Department of Neurology, University of Pennsylvania Perelman School of Medicine, Philadelphia, told delegates attending the 2024 annual meeting of the American Academy of Neurology. 
 

Significant Results

Investigators enrolled 58 children and adolescents with acute status migrainosus. The mean age was 16 years, and reported gender was female for 44 participants, male for 11 participants, and nonbinary or transgender in 3 participants. Participants had a migraine flare duration of 22 days and had not responded to other treatments. 

All participants had topical lidocaine cream applied for 30 minutes as a run-in step and could decline injections if they experienced sufficient benefit from cream alone. 

“We used a lidocaine cream lead-in for two reasons. One was to try to see if we could address the issue of high placebo response in pediatric trials in particular, and also to see if we could help with blinding to injection,” said Dr. Szperka. 

Topical lidocaine cream led to a small decrease in pain score overall (0.2 point on a 0-10 scale), and all participants proceeded to randomized blinded bilateral greater occipital nerve injection with 2% lidocaine or saline, she reported. 

On the primary endpoint — change in pain score at 30 minutes — lidocaine was significantly more effective than saline, achieving a 2.3-point decrease on average (on a 0-10 scale) vs a 1.1-point decrease with saline (P = .01).

A 2-point pain reduction was achieved in 69% of patients in the lidocaine group versus 34% in the saline group.

Three quarters (76%) of patients getting lidocaine reported at least partial relief in severity or location of pain compared with 48% of those getting saline (P = .03). Rates of pain freedom at 30 minutes were 17% and 7%, respectively, and at 24 hours were 14% and 0%, respectively.

The majority of adverse events were mild and fairly equal across groups and included anxiety, worsening headache, injection site pain, dizziness, and numbness (more so with lidocaine). There was one case of anaphylaxis after lidocaine injection.

Quite unexpectedly, said Dr. Szperka, patients rated the saline injection as more painful than the lidocaine injection. “This was not what I expected going in, and I think is relevant for future trials,” she said.
 

Encouraging Results 

Reached for comment, Shaheen Lakhan, MD, a neurologist and researcher based in Miami, said that as a neurologist and pain physician, he sees firsthand the “devastating impact of status migrainosus on children.”

“These debilitating headaches can rob them of precious school days, hindering learning and social interaction,” said Dr. Lakhan. “The constant pain and fear of the next attack can also take a toll on their emotional well-being.”

The impact on families is significant as well, highlighting the need to find more effective treatments, Dr. Lakhan said. 

“Traditionally, we’ve relied on case studies to see the benefits of nerve blocks for migraine in younger patients. This is the first randomized controlled trial that shows lidocaine injections can be significantly more effective than a placebo for these unrelenting migraines,” he said.

“It’s important to note that this is a relatively small study, and not without safety concerns, including rare but potentially life-threatening anaphylaxis to lidocaine,” Dr. Lakhan added. “More research is needed, but these findings are encouraging. Lidocaine injections could become a valuable tool for managing treatment-resistant migraines in adolescents and young adults.”

The study was supported by a grant from the National Institute of Neurological Disorders and Stroke. Dr. Szperka is a consultant for AbbVie and Teva; serves on a Data Safety Monitoring Board for Eli Lilly and Upsher-Smith; and is a site principal investigator for AbbVie, Amgen, Biohaven/Pfizer, Teva, and Theranica. Dr. Lakhan had no disclosures.
 

A version of this article appeared on Medscape.com.

DENVER — Lidocaine injections into the greater occipital nerve relieve severe, refractory migraine attacks in children, results of a randomized controlled trial show. 

Investigators found children receiving bilateral occipital nerve blocks with 2% lidocaine had significantly greater pain relief than that of peers receiving saline injections. 

Cases series have shown a benefit of peripheral nerve blocks (PNBs) — injections of local anesthetics over branches of the occipital or trigeminal nerve — for severe, refractory headache in children.  

Although 80% of pediatric headache specialists use PNBs, there is “inconsistent insurance coverage” for this treatment, which had not been tested in a randomized controlled trial in children before now, lead investigator Christina Szperka, MD, with the Pediatric Headache Program, Department of Neurology, University of Pennsylvania Perelman School of Medicine, Philadelphia, told delegates attending the 2024 annual meeting of the American Academy of Neurology. 
 

Significant Results

Investigators enrolled 58 children and adolescents with acute status migrainosus. The mean age was 16 years, and reported gender was female for 44 participants, male for 11 participants, and nonbinary or transgender in 3 participants. Participants had a migraine flare duration of 22 days and had not responded to other treatments. 

All participants had topical lidocaine cream applied for 30 minutes as a run-in step and could decline injections if they experienced sufficient benefit from cream alone. 

“We used a lidocaine cream lead-in for two reasons. One was to try to see if we could address the issue of high placebo response in pediatric trials in particular, and also to see if we could help with blinding to injection,” said Dr. Szperka. 

Topical lidocaine cream led to a small decrease in pain score overall (0.2 point on a 0-10 scale), and all participants proceeded to randomized blinded bilateral greater occipital nerve injection with 2% lidocaine or saline, she reported. 

On the primary endpoint — change in pain score at 30 minutes — lidocaine was significantly more effective than saline, achieving a 2.3-point decrease on average (on a 0-10 scale) vs a 1.1-point decrease with saline (P = .01).

A 2-point pain reduction was achieved in 69% of patients in the lidocaine group versus 34% in the saline group.

Three quarters (76%) of patients getting lidocaine reported at least partial relief in severity or location of pain compared with 48% of those getting saline (P = .03). Rates of pain freedom at 30 minutes were 17% and 7%, respectively, and at 24 hours were 14% and 0%, respectively.

The majority of adverse events were mild and fairly equal across groups and included anxiety, worsening headache, injection site pain, dizziness, and numbness (more so with lidocaine). There was one case of anaphylaxis after lidocaine injection.

Quite unexpectedly, said Dr. Szperka, patients rated the saline injection as more painful than the lidocaine injection. “This was not what I expected going in, and I think is relevant for future trials,” she said.
 

Encouraging Results 

Reached for comment, Shaheen Lakhan, MD, a neurologist and researcher based in Miami, said that as a neurologist and pain physician, he sees firsthand the “devastating impact of status migrainosus on children.”

“These debilitating headaches can rob them of precious school days, hindering learning and social interaction,” said Dr. Lakhan. “The constant pain and fear of the next attack can also take a toll on their emotional well-being.”

The impact on families is significant as well, highlighting the need to find more effective treatments, Dr. Lakhan said. 

“Traditionally, we’ve relied on case studies to see the benefits of nerve blocks for migraine in younger patients. This is the first randomized controlled trial that shows lidocaine injections can be significantly more effective than a placebo for these unrelenting migraines,” he said.

“It’s important to note that this is a relatively small study, and not without safety concerns, including rare but potentially life-threatening anaphylaxis to lidocaine,” Dr. Lakhan added. “More research is needed, but these findings are encouraging. Lidocaine injections could become a valuable tool for managing treatment-resistant migraines in adolescents and young adults.”

The study was supported by a grant from the National Institute of Neurological Disorders and Stroke. Dr. Szperka is a consultant for AbbVie and Teva; serves on a Data Safety Monitoring Board for Eli Lilly and Upsher-Smith; and is a site principal investigator for AbbVie, Amgen, Biohaven/Pfizer, Teva, and Theranica. Dr. Lakhan had no disclosures.
 

A version of this article appeared on Medscape.com.

DENVER — Intravenous (IV) ketamine is an effective and safe treatment option for children with severe refractory headache, new research suggests. In a retrospective chart review, IV ketamine led to in a 50% reduction in pain at discharge, with “nearly two-thirds” of patients having no recurrence within 30 days, noted lead investigator Scott Rosenthal, MD, from the University of Colorado Anschutz Medical Campus, Aurora.

Dr. Rosenthal reported the findings at the 2024 annual meeting of the American Academy of Neurology.
 

Statistically Significant Pain Relief

“IV ketamine has shown benefit in nonheadache chronic pain syndromes and refractory mood disorders. Patients with refractory status migraines are often left with ongoing pain and dysfunction after failing typical interventions,” Dr. Rosenthal said. 

“Ketamine has emerged as a potential treatment option in this population. However, there’s very little research on the efficacy and tolerability of it in general as well as the pediatric population,” he noted. 

Dr. Rosenthal and colleagues took a look back at patients admitted to Children’s Hospital Colorado between 2019 and 2022 for treatment of severe refractory headache who were treated with continuous IV ketamine. 

They analyzed 68 encounters of 41 unique patients aged 5-21 years (median age 16 years; 85% girls). Chronic migraine without aura made up 79% of cases. 

On presentation, most patients had an exacerbation or ongoing worsening of pain for about 10 days, and all but two were taking a preventive medication. Nearly 70% had a comorbid psychiatric diagnosis such as anxiety or depression, and 60% had a comorbid chronic pain diagnosis separate from their headache diagnosis. 

The primary outcome was percent pain reduction at discharge and headache recurrence within 72 hours, with headache recurrence defined as receipt of neurology care via phone, clinic, or hospital encounter. 

Patients received IV ketamine at a median dose of 0.25 mg/kg/hr for a median of 3 days.

Overall, the treatment was “safe and well tolerated,” Dr. Rosenthal said. 

There were no serious adverse events and no cardiac side effects; 7% (five out of 68) stopped treatment due to side effects. The most common side effects were dizziness (23%), nausea (16%), blurred vision (12%), hallucinations (19%), cognitive fog (7%), vomiting (6%) and dysphoria (4%), worsening headache (4%), and paresthesia and cramping (1.5%).
 

‘Exciting Starting Point’

At baseline, pain scores were 8 (on a scale of 0-10) and progressively fell (improved) during treatment. Pain scores were 6 on day 1 and were 5 on day 2, with a slight rebound to 5 at discharge, although the pain reduction at discharge (vs baseline) remained statistically significant (P < .001). 

“The median percent pain reduction after 3 days of ketamine was about 40%,” Dr. Rosenthal said. 

He noted that on the first day of treatment, 16% of patients responded to treatment (with a > 50% reduction in their initial pain); this doubled to 33% on day 2 and increased to 44% at discharge. 

In terms of recurrence, 38% had a recurrence within 1 month, “meaning two thirds did not,” Dr. Rosenthal noted. Median time to recurrence was 7 days. There were no recurrences within 72 hours. 

The researchers also tried to tease out which patients might respond best to ketamine.

“Surprisingly,” there wasn’t a strong effect of most demographic variables such as age, sex, gender identity, chronic pain, psychiatric comorbidities, duration of headache, or prior interventions, Dr. Rosenthal noted. 

“Interestingly,” he said, patients who were on two or more preventive medications had a 50% reduction in their pain at discharge compared with a 33% reduction in patients taking one or no preventive medication. It’s possible that more preventative medications may “prime” a patient’s response to ketamine, Dr. Rosenthal said. 

She added that future randomized studies are needed to further assess IV ketamine for refractory headache in children, but these results are “an exciting starting point.” 
 

‘Still an Unknown’

Seniha Nur Ozudogru, MD, assistant professor of clinical neurology at Penn Medicine in Philadelphia, echoed the need for further study.

The role of IV ketamine in refractory pediatric headache is “still an unknown,” said Dr. Ozudogru, who was not involved in the study. 

She noted that currently, there is “no standard protocol for ketamine infusion, even for adults. Every institution has their own protocols, which makes it difficult.” 

Dr. Ozudogru also wonders how “doable” in-hospital IV infusions over 3 days may be for children. 

“Especially for chronic migraine patients, it can be really tricky to manage expectations in that even if they don’t respond and the headache doesn’t go away, they still may have to be discharged. That requires a specific approach and discussion with the patients,” Dr. Ozudogru said. 

Intranasal ketamine is another potential option, she said, with a recent study suggesting that intranasal ketamine is an effective treatment for children hospitalized with refractory migraine. 

“However, there is some concern about the potential of addiction and the side effects of hallucinations and what the main protocol will be, so this not a standard treatment and has to be studied further,” she said. 

The study had no specific funding. Dr. Rosenthal and Dr. Ozudogru have no relevant disclosures.
 

A version of this article appeared on Medscape.com.

DENVER — Intravenous (IV) ketamine is an effective and safe treatment option for children with severe refractory headache, new research suggests. In a retrospective chart review, IV ketamine led to in a 50% reduction in pain at discharge, with “nearly two-thirds” of patients having no recurrence within 30 days, noted lead investigator Scott Rosenthal, MD, from the University of Colorado Anschutz Medical Campus, Aurora.

Dr. Rosenthal reported the findings at the 2024 annual meeting of the American Academy of Neurology.
 

Statistically Significant Pain Relief

“IV ketamine has shown benefit in nonheadache chronic pain syndromes and refractory mood disorders. Patients with refractory status migraines are often left with ongoing pain and dysfunction after failing typical interventions,” Dr. Rosenthal said. 

“Ketamine has emerged as a potential treatment option in this population. However, there’s very little research on the efficacy and tolerability of it in general as well as the pediatric population,” he noted. 

Dr. Rosenthal and colleagues took a look back at patients admitted to Children’s Hospital Colorado between 2019 and 2022 for treatment of severe refractory headache who were treated with continuous IV ketamine. 

They analyzed 68 encounters of 41 unique patients aged 5-21 years (median age 16 years; 85% girls). Chronic migraine without aura made up 79% of cases. 

On presentation, most patients had an exacerbation or ongoing worsening of pain for about 10 days, and all but two were taking a preventive medication. Nearly 70% had a comorbid psychiatric diagnosis such as anxiety or depression, and 60% had a comorbid chronic pain diagnosis separate from their headache diagnosis. 

The primary outcome was percent pain reduction at discharge and headache recurrence within 72 hours, with headache recurrence defined as receipt of neurology care via phone, clinic, or hospital encounter. 

Patients received IV ketamine at a median dose of 0.25 mg/kg/hr for a median of 3 days.

Overall, the treatment was “safe and well tolerated,” Dr. Rosenthal said. 

There were no serious adverse events and no cardiac side effects; 7% (five out of 68) stopped treatment due to side effects. The most common side effects were dizziness (23%), nausea (16%), blurred vision (12%), hallucinations (19%), cognitive fog (7%), vomiting (6%) and dysphoria (4%), worsening headache (4%), and paresthesia and cramping (1.5%).
 

‘Exciting Starting Point’

At baseline, pain scores were 8 (on a scale of 0-10) and progressively fell (improved) during treatment. Pain scores were 6 on day 1 and were 5 on day 2, with a slight rebound to 5 at discharge, although the pain reduction at discharge (vs baseline) remained statistically significant (P < .001). 

“The median percent pain reduction after 3 days of ketamine was about 40%,” Dr. Rosenthal said. 

He noted that on the first day of treatment, 16% of patients responded to treatment (with a > 50% reduction in their initial pain); this doubled to 33% on day 2 and increased to 44% at discharge. 

In terms of recurrence, 38% had a recurrence within 1 month, “meaning two thirds did not,” Dr. Rosenthal noted. Median time to recurrence was 7 days. There were no recurrences within 72 hours. 

The researchers also tried to tease out which patients might respond best to ketamine.

“Surprisingly,” there wasn’t a strong effect of most demographic variables such as age, sex, gender identity, chronic pain, psychiatric comorbidities, duration of headache, or prior interventions, Dr. Rosenthal noted. 

“Interestingly,” he said, patients who were on two or more preventive medications had a 50% reduction in their pain at discharge compared with a 33% reduction in patients taking one or no preventive medication. It’s possible that more preventative medications may “prime” a patient’s response to ketamine, Dr. Rosenthal said. 

She added that future randomized studies are needed to further assess IV ketamine for refractory headache in children, but these results are “an exciting starting point.” 
 

‘Still an Unknown’

Seniha Nur Ozudogru, MD, assistant professor of clinical neurology at Penn Medicine in Philadelphia, echoed the need for further study.

The role of IV ketamine in refractory pediatric headache is “still an unknown,” said Dr. Ozudogru, who was not involved in the study. 

She noted that currently, there is “no standard protocol for ketamine infusion, even for adults. Every institution has their own protocols, which makes it difficult.” 

Dr. Ozudogru also wonders how “doable” in-hospital IV infusions over 3 days may be for children. 

“Especially for chronic migraine patients, it can be really tricky to manage expectations in that even if they don’t respond and the headache doesn’t go away, they still may have to be discharged. That requires a specific approach and discussion with the patients,” Dr. Ozudogru said. 

Intranasal ketamine is another potential option, she said, with a recent study suggesting that intranasal ketamine is an effective treatment for children hospitalized with refractory migraine. 

“However, there is some concern about the potential of addiction and the side effects of hallucinations and what the main protocol will be, so this not a standard treatment and has to be studied further,” she said. 

The study had no specific funding. Dr. Rosenthal and Dr. Ozudogru have no relevant disclosures.
 

A version of this article appeared on Medscape.com.

DENVER — Intravenous (IV) ketamine is an effective and safe treatment option for children with severe refractory headache, new research suggests. In a retrospective chart review, IV ketamine led to in a 50% reduction in pain at discharge, with “nearly two-thirds” of patients having no recurrence within 30 days, noted lead investigator Scott Rosenthal, MD, from the University of Colorado Anschutz Medical Campus, Aurora.

Dr. Rosenthal reported the findings at the 2024 annual meeting of the American Academy of Neurology.
 

Statistically Significant Pain Relief

“IV ketamine has shown benefit in nonheadache chronic pain syndromes and refractory mood disorders. Patients with refractory status migraines are often left with ongoing pain and dysfunction after failing typical interventions,” Dr. Rosenthal said. 

“Ketamine has emerged as a potential treatment option in this population. However, there’s very little research on the efficacy and tolerability of it in general as well as the pediatric population,” he noted. 

Dr. Rosenthal and colleagues took a look back at patients admitted to Children’s Hospital Colorado between 2019 and 2022 for treatment of severe refractory headache who were treated with continuous IV ketamine. 

They analyzed 68 encounters of 41 unique patients aged 5-21 years (median age 16 years; 85% girls). Chronic migraine without aura made up 79% of cases. 

On presentation, most patients had an exacerbation or ongoing worsening of pain for about 10 days, and all but two were taking a preventive medication. Nearly 70% had a comorbid psychiatric diagnosis such as anxiety or depression, and 60% had a comorbid chronic pain diagnosis separate from their headache diagnosis. 

The primary outcome was percent pain reduction at discharge and headache recurrence within 72 hours, with headache recurrence defined as receipt of neurology care via phone, clinic, or hospital encounter. 

Patients received IV ketamine at a median dose of 0.25 mg/kg/hr for a median of 3 days.

Overall, the treatment was “safe and well tolerated,” Dr. Rosenthal said. 

There were no serious adverse events and no cardiac side effects; 7% (five out of 68) stopped treatment due to side effects. The most common side effects were dizziness (23%), nausea (16%), blurred vision (12%), hallucinations (19%), cognitive fog (7%), vomiting (6%) and dysphoria (4%), worsening headache (4%), and paresthesia and cramping (1.5%).
 

‘Exciting Starting Point’

At baseline, pain scores were 8 (on a scale of 0-10) and progressively fell (improved) during treatment. Pain scores were 6 on day 1 and were 5 on day 2, with a slight rebound to 5 at discharge, although the pain reduction at discharge (vs baseline) remained statistically significant (P < .001). 

“The median percent pain reduction after 3 days of ketamine was about 40%,” Dr. Rosenthal said. 

He noted that on the first day of treatment, 16% of patients responded to treatment (with a > 50% reduction in their initial pain); this doubled to 33% on day 2 and increased to 44% at discharge. 

In terms of recurrence, 38% had a recurrence within 1 month, “meaning two thirds did not,” Dr. Rosenthal noted. Median time to recurrence was 7 days. There were no recurrences within 72 hours. 

The researchers also tried to tease out which patients might respond best to ketamine.

“Surprisingly,” there wasn’t a strong effect of most demographic variables such as age, sex, gender identity, chronic pain, psychiatric comorbidities, duration of headache, or prior interventions, Dr. Rosenthal noted. 

“Interestingly,” he said, patients who were on two or more preventive medications had a 50% reduction in their pain at discharge compared with a 33% reduction in patients taking one or no preventive medication. It’s possible that more preventative medications may “prime” a patient’s response to ketamine, Dr. Rosenthal said. 

She added that future randomized studies are needed to further assess IV ketamine for refractory headache in children, but these results are “an exciting starting point.” 
 

‘Still an Unknown’

Seniha Nur Ozudogru, MD, assistant professor of clinical neurology at Penn Medicine in Philadelphia, echoed the need for further study.

The role of IV ketamine in refractory pediatric headache is “still an unknown,” said Dr. Ozudogru, who was not involved in the study. 

She noted that currently, there is “no standard protocol for ketamine infusion, even for adults. Every institution has their own protocols, which makes it difficult.” 

Dr. Ozudogru also wonders how “doable” in-hospital IV infusions over 3 days may be for children. 

“Especially for chronic migraine patients, it can be really tricky to manage expectations in that even if they don’t respond and the headache doesn’t go away, they still may have to be discharged. That requires a specific approach and discussion with the patients,” Dr. Ozudogru said. 

Intranasal ketamine is another potential option, she said, with a recent study suggesting that intranasal ketamine is an effective treatment for children hospitalized with refractory migraine. 

“However, there is some concern about the potential of addiction and the side effects of hallucinations and what the main protocol will be, so this not a standard treatment and has to be studied further,” she said. 

The study had no specific funding. Dr. Rosenthal and Dr. Ozudogru have no relevant disclosures.
 

A version of this article appeared on Medscape.com.

DENVER – Headaches, including tension-type, migraine, and posttraumatic, are robustly associated with both attempted and completed suicide, results of a large study suggest. 

The risk for suicide attempt was four times higher in people with trigeminal and autonomic cephalalgias (TAC), and the risk for completed suicide was double among those with posttraumatic headache compared with individuals with no headache.

The retrospective analysis included data on more than 100,000 headache patients from a Danish registry. 

“The results suggest there’s a unique risk among headache patients for attempted and completed suicide,” lead investigator Holly Elser, MD, MPH, PhD, resident, Department of Neurology, University of Pennsylvania, Philadelphia, said at the 2024 annual meeting of the American Academy of Neurology, where the findings were presented. “This really underscores the potential importance of complementary psychiatric evaluation and treatment for individuals diagnosed with headache.”
 

Underestimated Problem

Headache disorders affect about half of working-age adults and are among the leading causes of productivity loss, absence from work, and disability. 

Prior research suggests headache disorders often co-occur with psychiatric illness including depression, anxiety, posttraumatic stress disorder, and even attempted suicide.

However, previous studies that showed an increased risk for attempted suicide in patients with headache relied heavily on survey data and mostly focused on patients with migraine. There was little information on other headache types and on the risk for completed suicide.

Researchers used Danish registries to identify 64,057 patients with migraine, 40,160 with tension-type headache (TTH), 5743 with TAC, and 4253 with posttraumatic headache, all diagnosed from 1995 to 2019.

Some 5.8% of those with migraine, 6.3% with TAC, 7.2% with TTH, and 7.2% with posttraumatic headache, had a mood disorder (depression and anxiety combined) at baseline.

Those without a headache diagnosis were matched 5:1 to those with a headache diagnosis by sex and birth year.

Across all headache disorders, baseline prevalence of mood disorder was higher among those with headache versus population-matched controls. Dr. Elser emphasized that these are people diagnosed with a mood disorder in the inpatient, emergency department, or outpatient specialist clinic setting, “which means we are almost certainly underestimating the true burden of mood symptoms in our cohort,” she said.

Researchers identified attempted suicides using diagnostic codes. For completed suicide, they determined whether those who attempted suicide died within 30 days of the attempt.

For each headache type, investigators examined both the absolute and relative risk for attempted and completed suicides and estimated the risk at intervals of 5, 10, and 20 years after initial headache diagnosis.
 

Robust Link

The “power of this study is that we asked a simple, but important question, and answered it with simple, but appropriate, methodologic techniques,” Dr. Elser said.

The estimated risk differences (RDs) for attempted suicide were strongest for TAC and posttraumatic headache and for longer follow-ups. The RDs for completed suicide were largely the same but of a smaller magnitude and were “relatively less precise,” reflecting the “rarity of this outcome,” said Dr. Elser.

After adjusting for sex, age, education, income, comorbidities, and baseline medical and psychiatric diagnoses, researchers found the strongest association or attempted suicide was among those with TAC (adjusted hazard ratio [aHR], 4.25; 95% CI, 2.85-6.33).

“A hazard ratio of 4 is enormous” for this type of comparison, Dr. Elser noted.

For completed suicide, the strongest association was with posttraumatic headache (aHR, 2.19; 95% CI, 0.78-6.16).

The study revealed a robust association with attempted and completed suicide across all headache types, including TTH, noted Dr. Elser. The link between tension headaches and suicide “was the most striking finding to me because I think of that as sort of a benign and common headache disorder,” she said.

The was an observational study, so “it’s not clear whether headache is playing an etiological role in the relationship with suicide,” she said. “It’s possible there are common shared risk factors or confounders that explain the relationship in full or in part that aren’t accounted for in this study.”
 

Ask About Mood

The results underscore the need for psychiatric evaluations in patients with a headache disorder. “For me, this is just going to make me that much more likely to ask my patients about their mood when I see them in clinic,” Dr. Elser said.

After asking patients with headache about their mood and stress at home and at work, physicians should have a “low threshold to refer to a behavioral health provider,” she added.

Future research should aim to better understand the link between headache and suicide risk, with a focus on the mechanisms behind low- and high-risk subgroups, said Dr. Elser.

A limitation of the study was that headache diagnoses were based on inpatient, emergency department, and outpatient specialist visits but not on visits to primary care practitioners. The study didn’t include information on headache severity or frequency and included only people who sought treatment for their headaches.

Though it’s unlikely the results “are perfectly generalizable” with respect to other geographical or cultural contexts, “I don’t think this relationship is unique to Denmark based on the literature to date,” Dr. Elser said.

Commenting on the study, session co-chair Todd J. Schwedt, MD, professor of neurology, Mayo Clinic Arizona, Phoenix, and president-elect of the American Headache Society, noted that the study offers important findings “that demonstrate the enormous negative impact that headaches can exert.”

It’s “a strong reminder” that clinicians should assess the mental health of their patients with headaches and offer treatment when appropriate, he said.

The study received support from Aarhus University. No relevant conflicts of interest were reported.
 

A version of this article appeared on Medscape.com.

DENVER – Headaches, including tension-type, migraine, and posttraumatic, are robustly associated with both attempted and completed suicide, results of a large study suggest. 

The risk for suicide attempt was four times higher in people with trigeminal and autonomic cephalalgias (TAC), and the risk for completed suicide was double among those with posttraumatic headache compared with individuals with no headache.

The retrospective analysis included data on more than 100,000 headache patients from a Danish registry. 

“The results suggest there’s a unique risk among headache patients for attempted and completed suicide,” lead investigator Holly Elser, MD, MPH, PhD, resident, Department of Neurology, University of Pennsylvania, Philadelphia, said at the 2024 annual meeting of the American Academy of Neurology, where the findings were presented. “This really underscores the potential importance of complementary psychiatric evaluation and treatment for individuals diagnosed with headache.”
 

Underestimated Problem

Headache disorders affect about half of working-age adults and are among the leading causes of productivity loss, absence from work, and disability. 

Prior research suggests headache disorders often co-occur with psychiatric illness including depression, anxiety, posttraumatic stress disorder, and even attempted suicide.

However, previous studies that showed an increased risk for attempted suicide in patients with headache relied heavily on survey data and mostly focused on patients with migraine. There was little information on other headache types and on the risk for completed suicide.

Researchers used Danish registries to identify 64,057 patients with migraine, 40,160 with tension-type headache (TTH), 5743 with TAC, and 4253 with posttraumatic headache, all diagnosed from 1995 to 2019.

Some 5.8% of those with migraine, 6.3% with TAC, 7.2% with TTH, and 7.2% with posttraumatic headache, had a mood disorder (depression and anxiety combined) at baseline.

Those without a headache diagnosis were matched 5:1 to those with a headache diagnosis by sex and birth year.

Across all headache disorders, baseline prevalence of mood disorder was higher among those with headache versus population-matched controls. Dr. Elser emphasized that these are people diagnosed with a mood disorder in the inpatient, emergency department, or outpatient specialist clinic setting, “which means we are almost certainly underestimating the true burden of mood symptoms in our cohort,” she said.

Researchers identified attempted suicides using diagnostic codes. For completed suicide, they determined whether those who attempted suicide died within 30 days of the attempt.

For each headache type, investigators examined both the absolute and relative risk for attempted and completed suicides and estimated the risk at intervals of 5, 10, and 20 years after initial headache diagnosis.
 

Robust Link

The “power of this study is that we asked a simple, but important question, and answered it with simple, but appropriate, methodologic techniques,” Dr. Elser said.

The estimated risk differences (RDs) for attempted suicide were strongest for TAC and posttraumatic headache and for longer follow-ups. The RDs for completed suicide were largely the same but of a smaller magnitude and were “relatively less precise,” reflecting the “rarity of this outcome,” said Dr. Elser.

After adjusting for sex, age, education, income, comorbidities, and baseline medical and psychiatric diagnoses, researchers found the strongest association or attempted suicide was among those with TAC (adjusted hazard ratio [aHR], 4.25; 95% CI, 2.85-6.33).

“A hazard ratio of 4 is enormous” for this type of comparison, Dr. Elser noted.

For completed suicide, the strongest association was with posttraumatic headache (aHR, 2.19; 95% CI, 0.78-6.16).

The study revealed a robust association with attempted and completed suicide across all headache types, including TTH, noted Dr. Elser. The link between tension headaches and suicide “was the most striking finding to me because I think of that as sort of a benign and common headache disorder,” she said.

The was an observational study, so “it’s not clear whether headache is playing an etiological role in the relationship with suicide,” she said. “It’s possible there are common shared risk factors or confounders that explain the relationship in full or in part that aren’t accounted for in this study.”
 

Ask About Mood

The results underscore the need for psychiatric evaluations in patients with a headache disorder. “For me, this is just going to make me that much more likely to ask my patients about their mood when I see them in clinic,” Dr. Elser said.

After asking patients with headache about their mood and stress at home and at work, physicians should have a “low threshold to refer to a behavioral health provider,” she added.

Future research should aim to better understand the link between headache and suicide risk, with a focus on the mechanisms behind low- and high-risk subgroups, said Dr. Elser.

A limitation of the study was that headache diagnoses were based on inpatient, emergency department, and outpatient specialist visits but not on visits to primary care practitioners. The study didn’t include information on headache severity or frequency and included only people who sought treatment for their headaches.

Though it’s unlikely the results “are perfectly generalizable” with respect to other geographical or cultural contexts, “I don’t think this relationship is unique to Denmark based on the literature to date,” Dr. Elser said.

Commenting on the study, session co-chair Todd J. Schwedt, MD, professor of neurology, Mayo Clinic Arizona, Phoenix, and president-elect of the American Headache Society, noted that the study offers important findings “that demonstrate the enormous negative impact that headaches can exert.”

It’s “a strong reminder” that clinicians should assess the mental health of their patients with headaches and offer treatment when appropriate, he said.

The study received support from Aarhus University. No relevant conflicts of interest were reported.
 

A version of this article appeared on Medscape.com.

DENVER – Headaches, including tension-type, migraine, and posttraumatic, are robustly associated with both attempted and completed suicide, results of a large study suggest. 

The risk for suicide attempt was four times higher in people with trigeminal and autonomic cephalalgias (TAC), and the risk for completed suicide was double among those with posttraumatic headache compared with individuals with no headache.

The retrospective analysis included data on more than 100,000 headache patients from a Danish registry. 

“The results suggest there’s a unique risk among headache patients for attempted and completed suicide,” lead investigator Holly Elser, MD, MPH, PhD, resident, Department of Neurology, University of Pennsylvania, Philadelphia, said at the 2024 annual meeting of the American Academy of Neurology, where the findings were presented. “This really underscores the potential importance of complementary psychiatric evaluation and treatment for individuals diagnosed with headache.”
 

Underestimated Problem

Headache disorders affect about half of working-age adults and are among the leading causes of productivity loss, absence from work, and disability. 

Prior research suggests headache disorders often co-occur with psychiatric illness including depression, anxiety, posttraumatic stress disorder, and even attempted suicide.

However, previous studies that showed an increased risk for attempted suicide in patients with headache relied heavily on survey data and mostly focused on patients with migraine. There was little information on other headache types and on the risk for completed suicide.

Researchers used Danish registries to identify 64,057 patients with migraine, 40,160 with tension-type headache (TTH), 5743 with TAC, and 4253 with posttraumatic headache, all diagnosed from 1995 to 2019.

Some 5.8% of those with migraine, 6.3% with TAC, 7.2% with TTH, and 7.2% with posttraumatic headache, had a mood disorder (depression and anxiety combined) at baseline.

Those without a headache diagnosis were matched 5:1 to those with a headache diagnosis by sex and birth year.

Across all headache disorders, baseline prevalence of mood disorder was higher among those with headache versus population-matched controls. Dr. Elser emphasized that these are people diagnosed with a mood disorder in the inpatient, emergency department, or outpatient specialist clinic setting, “which means we are almost certainly underestimating the true burden of mood symptoms in our cohort,” she said.

Researchers identified attempted suicides using diagnostic codes. For completed suicide, they determined whether those who attempted suicide died within 30 days of the attempt.

For each headache type, investigators examined both the absolute and relative risk for attempted and completed suicides and estimated the risk at intervals of 5, 10, and 20 years after initial headache diagnosis.
 

Robust Link

The “power of this study is that we asked a simple, but important question, and answered it with simple, but appropriate, methodologic techniques,” Dr. Elser said.

The estimated risk differences (RDs) for attempted suicide were strongest for TAC and posttraumatic headache and for longer follow-ups. The RDs for completed suicide were largely the same but of a smaller magnitude and were “relatively less precise,” reflecting the “rarity of this outcome,” said Dr. Elser.

After adjusting for sex, age, education, income, comorbidities, and baseline medical and psychiatric diagnoses, researchers found the strongest association or attempted suicide was among those with TAC (adjusted hazard ratio [aHR], 4.25; 95% CI, 2.85-6.33).

“A hazard ratio of 4 is enormous” for this type of comparison, Dr. Elser noted.

For completed suicide, the strongest association was with posttraumatic headache (aHR, 2.19; 95% CI, 0.78-6.16).

The study revealed a robust association with attempted and completed suicide across all headache types, including TTH, noted Dr. Elser. The link between tension headaches and suicide “was the most striking finding to me because I think of that as sort of a benign and common headache disorder,” she said.

The was an observational study, so “it’s not clear whether headache is playing an etiological role in the relationship with suicide,” she said. “It’s possible there are common shared risk factors or confounders that explain the relationship in full or in part that aren’t accounted for in this study.”
 

Ask About Mood

The results underscore the need for psychiatric evaluations in patients with a headache disorder. “For me, this is just going to make me that much more likely to ask my patients about their mood when I see them in clinic,” Dr. Elser said.

After asking patients with headache about their mood and stress at home and at work, physicians should have a “low threshold to refer to a behavioral health provider,” she added.

Future research should aim to better understand the link between headache and suicide risk, with a focus on the mechanisms behind low- and high-risk subgroups, said Dr. Elser.

A limitation of the study was that headache diagnoses were based on inpatient, emergency department, and outpatient specialist visits but not on visits to primary care practitioners. The study didn’t include information on headache severity or frequency and included only people who sought treatment for their headaches.

Though it’s unlikely the results “are perfectly generalizable” with respect to other geographical or cultural contexts, “I don’t think this relationship is unique to Denmark based on the literature to date,” Dr. Elser said.

Commenting on the study, session co-chair Todd J. Schwedt, MD, professor of neurology, Mayo Clinic Arizona, Phoenix, and president-elect of the American Headache Society, noted that the study offers important findings “that demonstrate the enormous negative impact that headaches can exert.”

It’s “a strong reminder” that clinicians should assess the mental health of their patients with headaches and offer treatment when appropriate, he said.

The study received support from Aarhus University. No relevant conflicts of interest were reported.
 

A version of this article appeared on Medscape.com.

The consequences of chronic musculoskeletal pain (CMP) may extend well beyond physical discomfort, potentially leading to faster aging of the brain, new research showed.

Using structural MRI data from more than 9000 adults with knee osteoarthritis (KOA) from the UK Biobank, investigators developed a brain age model to compare an individual’s brain age with their chronological age. Those with KOA showed a much faster rate of brain aging than healthy individuals.

The acceleration in brain aging was largely driven by the hippocampus and predicted memory decline and incident dementia during follow-up. Researchers identified a gene highly expressed in glial cells as a possible genetic factor for accelerated brain aging.

“We demonstrate the accelerated brain aging and cognitive decline in chronic musculoskeletal pain, in particular knee osteoarthritis, and provide a neural marker for early detection and intervention,” said co-first author Jiao Liu, PhD candidate, Chinese Academy of Sciences, Beijing.

“We are interested to know how to slow down the aging brain in chronic musculoskeletal pain patients. Proper exercise and lifestyle may reduce the risk,” Dr. Liu said.

The study was published online in Nature Mental Health.
 

Common Condition

CMP affects more than 40% of the world’s population and has been shown to have a harmful impact on cognitive function, although the exact mechanisms remain unclear. Prior research suggests that inflammatory markers associated with brain aging are higher in patients with CMP, suggesting a link between brain aging and CMP.

To investigate further, researchers explored patterns of brain aging in healthy cohorts and cohorts with four common types of CMP — chronic knee pain, chronic back pain, chronic neck pain, and chronic hip pain.

Using their brain age model, investigators observed significantly increased brain aging, or “predicted age difference,” only in individuals with KOA (P < .001). The observation was validated in an independent dataset (P = .020), suggesting a pattern of brain aging acceleration specific to KOA.

This acceleration was primarily driven by key brain regions involved in cognitive processing, including hippocampus and orbitofrontal cortex, and was correlated with longitudinal memory decline and dementia risk.

These data also suggest that the SLC39A8 gene, which is highly expressed in glial cells, might be a key genetic factor underpinning this acceleration.

“We not only revealed the specificity of accelerated brain aging in knee osteoarthritis patients, but importantly, we also provided longitudinal evidence suggesting the ability of our brain aging marker to predict future memory decline and increased dementia risk,” corresponding author Yiheng Tu, PhD, also with Chinese Academy of Sciences, Beijing, said in a news release.
 

A Future Treatment Target?

Commenting on this research, Shaheen Lakhan, MD, PhD, a neurologist and researcher based in Miami, noted that in this study, people with KOA showed signs of “faster brain aging on scans. Think of it as your brain wearing a disguise, appearing older than its actual years,” Dr. Lakhan said.

“Inflammation, a key player in osteoarthritis, might be playing a double agent, wreaking havoc not just on your joints but potentially on your memory too. Researchers even identified a specific gene linked to both knee pain and faster brain aging, hinting at a potential target for future treatments,” he added.

“Importantly, the increased risk of cognitive decline and dementia associated with chronic pain is likely one of many factors, and probably not a very high one on its own,” Dr. Lakhan noted.

The “good news,” he said, is that there are many “well-established ways to keep your brain sharp. Regular exercise, a healthy diet, and staying mentally stimulated are all proven strategies to reduce dementia risk. Think of chronic pain management as another tool you can add to your brain health toolbox.”

Support for the study was provided by the STI-2030 Major Project, the National Natural Science Foundation of China, the Scientific Foundation of the Institute of Psychology, Chinese Academy of Sciences, and the Young Elite Scientist Sponsorship Program by the China Association for Science and Technology. Dr. Liu and Dr. Lakhan had no relevant disclosures.

A version of this article appeared on Medscape.com.

The consequences of chronic musculoskeletal pain (CMP) may extend well beyond physical discomfort, potentially leading to faster aging of the brain, new research showed.

Using structural MRI data from more than 9000 adults with knee osteoarthritis (KOA) from the UK Biobank, investigators developed a brain age model to compare an individual’s brain age with their chronological age. Those with KOA showed a much faster rate of brain aging than healthy individuals.

The acceleration in brain aging was largely driven by the hippocampus and predicted memory decline and incident dementia during follow-up. Researchers identified a gene highly expressed in glial cells as a possible genetic factor for accelerated brain aging.

“We demonstrate the accelerated brain aging and cognitive decline in chronic musculoskeletal pain, in particular knee osteoarthritis, and provide a neural marker for early detection and intervention,” said co-first author Jiao Liu, PhD candidate, Chinese Academy of Sciences, Beijing.

“We are interested to know how to slow down the aging brain in chronic musculoskeletal pain patients. Proper exercise and lifestyle may reduce the risk,” Dr. Liu said.

The study was published online in Nature Mental Health.
 

Common Condition

CMP affects more than 40% of the world’s population and has been shown to have a harmful impact on cognitive function, although the exact mechanisms remain unclear. Prior research suggests that inflammatory markers associated with brain aging are higher in patients with CMP, suggesting a link between brain aging and CMP.

To investigate further, researchers explored patterns of brain aging in healthy cohorts and cohorts with four common types of CMP — chronic knee pain, chronic back pain, chronic neck pain, and chronic hip pain.

Using their brain age model, investigators observed significantly increased brain aging, or “predicted age difference,” only in individuals with KOA (P < .001). The observation was validated in an independent dataset (P = .020), suggesting a pattern of brain aging acceleration specific to KOA.

This acceleration was primarily driven by key brain regions involved in cognitive processing, including hippocampus and orbitofrontal cortex, and was correlated with longitudinal memory decline and dementia risk.

These data also suggest that the SLC39A8 gene, which is highly expressed in glial cells, might be a key genetic factor underpinning this acceleration.

“We not only revealed the specificity of accelerated brain aging in knee osteoarthritis patients, but importantly, we also provided longitudinal evidence suggesting the ability of our brain aging marker to predict future memory decline and increased dementia risk,” corresponding author Yiheng Tu, PhD, also with Chinese Academy of Sciences, Beijing, said in a news release.
 

A Future Treatment Target?

Commenting on this research, Shaheen Lakhan, MD, PhD, a neurologist and researcher based in Miami, noted that in this study, people with KOA showed signs of “faster brain aging on scans. Think of it as your brain wearing a disguise, appearing older than its actual years,” Dr. Lakhan said.

“Inflammation, a key player in osteoarthritis, might be playing a double agent, wreaking havoc not just on your joints but potentially on your memory too. Researchers even identified a specific gene linked to both knee pain and faster brain aging, hinting at a potential target for future treatments,” he added.

“Importantly, the increased risk of cognitive decline and dementia associated with chronic pain is likely one of many factors, and probably not a very high one on its own,” Dr. Lakhan noted.

The “good news,” he said, is that there are many “well-established ways to keep your brain sharp. Regular exercise, a healthy diet, and staying mentally stimulated are all proven strategies to reduce dementia risk. Think of chronic pain management as another tool you can add to your brain health toolbox.”

Support for the study was provided by the STI-2030 Major Project, the National Natural Science Foundation of China, the Scientific Foundation of the Institute of Psychology, Chinese Academy of Sciences, and the Young Elite Scientist Sponsorship Program by the China Association for Science and Technology. Dr. Liu and Dr. Lakhan had no relevant disclosures.

A version of this article appeared on Medscape.com.

The consequences of chronic musculoskeletal pain (CMP) may extend well beyond physical discomfort, potentially leading to faster aging of the brain, new research showed.

Using structural MRI data from more than 9000 adults with knee osteoarthritis (KOA) from the UK Biobank, investigators developed a brain age model to compare an individual’s brain age with their chronological age. Those with KOA showed a much faster rate of brain aging than healthy individuals.

The acceleration in brain aging was largely driven by the hippocampus and predicted memory decline and incident dementia during follow-up. Researchers identified a gene highly expressed in glial cells as a possible genetic factor for accelerated brain aging.

“We demonstrate the accelerated brain aging and cognitive decline in chronic musculoskeletal pain, in particular knee osteoarthritis, and provide a neural marker for early detection and intervention,” said co-first author Jiao Liu, PhD candidate, Chinese Academy of Sciences, Beijing.

“We are interested to know how to slow down the aging brain in chronic musculoskeletal pain patients. Proper exercise and lifestyle may reduce the risk,” Dr. Liu said.

The study was published online in Nature Mental Health.
 

Common Condition

CMP affects more than 40% of the world’s population and has been shown to have a harmful impact on cognitive function, although the exact mechanisms remain unclear. Prior research suggests that inflammatory markers associated with brain aging are higher in patients with CMP, suggesting a link between brain aging and CMP.

To investigate further, researchers explored patterns of brain aging in healthy cohorts and cohorts with four common types of CMP — chronic knee pain, chronic back pain, chronic neck pain, and chronic hip pain.

Using their brain age model, investigators observed significantly increased brain aging, or “predicted age difference,” only in individuals with KOA (P < .001). The observation was validated in an independent dataset (P = .020), suggesting a pattern of brain aging acceleration specific to KOA.

This acceleration was primarily driven by key brain regions involved in cognitive processing, including hippocampus and orbitofrontal cortex, and was correlated with longitudinal memory decline and dementia risk.

These data also suggest that the SLC39A8 gene, which is highly expressed in glial cells, might be a key genetic factor underpinning this acceleration.

“We not only revealed the specificity of accelerated brain aging in knee osteoarthritis patients, but importantly, we also provided longitudinal evidence suggesting the ability of our brain aging marker to predict future memory decline and increased dementia risk,” corresponding author Yiheng Tu, PhD, also with Chinese Academy of Sciences, Beijing, said in a news release.
 

A Future Treatment Target?

Commenting on this research, Shaheen Lakhan, MD, PhD, a neurologist and researcher based in Miami, noted that in this study, people with KOA showed signs of “faster brain aging on scans. Think of it as your brain wearing a disguise, appearing older than its actual years,” Dr. Lakhan said.

“Inflammation, a key player in osteoarthritis, might be playing a double agent, wreaking havoc not just on your joints but potentially on your memory too. Researchers even identified a specific gene linked to both knee pain and faster brain aging, hinting at a potential target for future treatments,” he added.

“Importantly, the increased risk of cognitive decline and dementia associated with chronic pain is likely one of many factors, and probably not a very high one on its own,” Dr. Lakhan noted.

The “good news,” he said, is that there are many “well-established ways to keep your brain sharp. Regular exercise, a healthy diet, and staying mentally stimulated are all proven strategies to reduce dementia risk. Think of chronic pain management as another tool you can add to your brain health toolbox.”

Support for the study was provided by the STI-2030 Major Project, the National Natural Science Foundation of China, the Scientific Foundation of the Institute of Psychology, Chinese Academy of Sciences, and the Young Elite Scientist Sponsorship Program by the China Association for Science and Technology. Dr. Liu and Dr. Lakhan had no relevant disclosures.

A version of this article appeared on Medscape.com.

A group of researchers urged US regulators to revoke the approval of a test marketed for predicting risk for opioid addiction and said government health plans should not pay for the product. 

The focus of the request is AdvertD (SOLVD Health), which the US Food and Drug Administration (FDA) approved in December as the first test to use DNA to evaluate if people have an elevated risk for opioid use disorder (OUD). A sample obtained through a cheek swab is meant to help guide decisions about opioid prescriptions for patients not previously treated with these drugs, such as someone undergoing a planned surgery, the FDA said. 

But Michael T. Abrams, MPH, PhD, senior health researcher for Public Citizen’s Health Research Group, and 30 other physicians and researchers sent an April 4 letter to the Food and Drug Administration calling on the government to reconsider. 

Dr. Abrams and fellow signers of the letters, including longtime opioid watchdog Andrew Kolodny, MD, of Brandeis University, said the algorithm used in creating AvertD “fell into known pitfalls of genetic prediction that give the appearance of predicting genetic risk, without being a true measure of genetic risk.” 

“The harmful consequences of an invalid genetic test for OUD are clear. Patients who test negative, and their clinicians, may have a false sense of security about use of opioids,” the letter states. 

The letter adds that false-positive test results may result in harmful consequences, with clinicians refraining from prescribing needed opioids, a problem that may be magnified in minority populations. 

Among the signers of the letter is Alexander Hatoum, PhD, of Washington University, who conducted an independent evaluation of AdvertD, which he and his colleagues published in 2021 in Drug and Alcohol Dependency. 

Dr. Hatoum said many patients may not fully understand the limit of genetic testing in predicting conditions like risk for OUD, where many factors are at play. The availability of a test may lend the impression that a single DNA trait makes the difference, as happens with conditions like Huntington’s disease and cystic fibrosis, he said. 

“But it’s just not reality for most diseases,” Dr. Hatoum told this news organization. 

The FDA declined to comment on the letter and said its approval of the test was “another step forward” in efforts to prevent new cases of OUD. 

In 2021, a little more than three quarters of people who died by overdose in the United States involved opioids, or more than 80,000 people, according to the US Centers for Disease Control and Prevention. This figure includes prescription opioids, heroin, and fentanyl. 

While deaths from overdoses with prescription opioids peaked in 2017 at 17,029 people, that figure has decreased steadily. Meanwhile, synthetic opioids other than methadone — primarily fentanyl — were the main driver of drug overdose deaths with a nearly 7.5-fold increase from 2015 to 2021. 

The FDA agency said it had “a reasonable assurance of AvertD’s safety and effectiveness, taking into consideration available alternatives, patients’ perspectives, the public health need and the ability to address uncertainty through the collection of post-market data.” 

Slow Rollout

In a separate letter to the Centers for Medicare and Medicaid Services, Dr. Abrams, Dr. Kolodny, Dr. Hatoum, and the other signers repeated their arguments against the use of AdvertD and asked that the government not use federal funds to pay for the test. 

SOLVD is not yet selling AdvertD in the United States, and it has not yet set a price for the product. The Carlsbad, California-based company told this news organization in an email exchange that it is working with both Medicare and private insurers on questions of future coverage. 

AvertD correctly identified an elevated risk for OUD in about 82.8% of cases, equating to a false-negative rate of 18.2% of patients, the FDA said in its summary of on the data supporting the application. This measure is known as sensitivity, meaning it shows how often an individual has the condition addressed in the test. 

Meanwhile, the false positive rate was 20.8%, the FDA said. 

SOLVD published similar study results in 2021. 

The company failed to impress the FDA’s Clinical Chemistry and Clinical Toxicology Devices Panel, which in October 2022, said the probable risks of the test likely outweighed its benefits. 

Then, in November 2022, the FDA and National Institutes of Health (NIH) held a public workshop meeting  to consider the challenges and possibilities in developing tools to predict the risk of developing OUD. At that meeting, Keri Donaldson, MD, MSCE, the chief executive officer of SOLVD, said the company planned to conduct a controlled rollout of AdvertD on FDA approval. 

Dr. Donaldson said a “defined set” of clinicians would first access the test, allowing the company to understand how results would be used in clinical practice.

“Once a test gets into practice, you have to be very purposeful and thoughtful about how it’s used,” he said.

The FDA approved the test in December 2023, saying it had worked with the company on modifications to its test. It also said that the advisory committee’s feedback helped in the evaluation and ultimate approval of AdvertD. 

Even beyond the debate about the predictive ability of genetic tests for OUD are larger questions that physicians need time to ask patients in assessing their potential risk for addiction when prescribing narcotic painkillers, said Maya Hambright, MD, a physician in New York’s Hudson Valley who has been working mainly in addiction in response to the overdose crisis. 

Genetics are just one of many factors at play in causing people to become addicted to opioids, Dr. Hambright said. 

Physicians must also consider the lasting effects of emotional and physical trauma experienced at any age, but particularly in childhood, as well as what kind of social support a patient has in facing the illness or injury that may require opioids for pain, she said. 

“There is a time and place for narcotic medications to be prescribed appropriately, which means we have to do our due diligence,” Dr. Hambright told this news organization. “Regardless of the strides we make in research and development, we still must connect and communicate safely and effectively and compassionately with our patients.” 

A version of this article appeared on Medscape.com.

A group of researchers urged US regulators to revoke the approval of a test marketed for predicting risk for opioid addiction and said government health plans should not pay for the product. 

The focus of the request is AdvertD (SOLVD Health), which the US Food and Drug Administration (FDA) approved in December as the first test to use DNA to evaluate if people have an elevated risk for opioid use disorder (OUD). A sample obtained through a cheek swab is meant to help guide decisions about opioid prescriptions for patients not previously treated with these drugs, such as someone undergoing a planned surgery, the FDA said. 

But Michael T. Abrams, MPH, PhD, senior health researcher for Public Citizen’s Health Research Group, and 30 other physicians and researchers sent an April 4 letter to the Food and Drug Administration calling on the government to reconsider. 

Dr. Abrams and fellow signers of the letters, including longtime opioid watchdog Andrew Kolodny, MD, of Brandeis University, said the algorithm used in creating AvertD “fell into known pitfalls of genetic prediction that give the appearance of predicting genetic risk, without being a true measure of genetic risk.” 

“The harmful consequences of an invalid genetic test for OUD are clear. Patients who test negative, and their clinicians, may have a false sense of security about use of opioids,” the letter states. 

The letter adds that false-positive test results may result in harmful consequences, with clinicians refraining from prescribing needed opioids, a problem that may be magnified in minority populations. 

Among the signers of the letter is Alexander Hatoum, PhD, of Washington University, who conducted an independent evaluation of AdvertD, which he and his colleagues published in 2021 in Drug and Alcohol Dependency. 

Dr. Hatoum said many patients may not fully understand the limit of genetic testing in predicting conditions like risk for OUD, where many factors are at play. The availability of a test may lend the impression that a single DNA trait makes the difference, as happens with conditions like Huntington’s disease and cystic fibrosis, he said. 

“But it’s just not reality for most diseases,” Dr. Hatoum told this news organization. 

The FDA declined to comment on the letter and said its approval of the test was “another step forward” in efforts to prevent new cases of OUD. 

In 2021, a little more than three quarters of people who died by overdose in the United States involved opioids, or more than 80,000 people, according to the US Centers for Disease Control and Prevention. This figure includes prescription opioids, heroin, and fentanyl. 

While deaths from overdoses with prescription opioids peaked in 2017 at 17,029 people, that figure has decreased steadily. Meanwhile, synthetic opioids other than methadone — primarily fentanyl — were the main driver of drug overdose deaths with a nearly 7.5-fold increase from 2015 to 2021. 

The FDA agency said it had “a reasonable assurance of AvertD’s safety and effectiveness, taking into consideration available alternatives, patients’ perspectives, the public health need and the ability to address uncertainty through the collection of post-market data.” 

Slow Rollout

In a separate letter to the Centers for Medicare and Medicaid Services, Dr. Abrams, Dr. Kolodny, Dr. Hatoum, and the other signers repeated their arguments against the use of AdvertD and asked that the government not use federal funds to pay for the test. 

SOLVD is not yet selling AdvertD in the United States, and it has not yet set a price for the product. The Carlsbad, California-based company told this news organization in an email exchange that it is working with both Medicare and private insurers on questions of future coverage. 

AvertD correctly identified an elevated risk for OUD in about 82.8% of cases, equating to a false-negative rate of 18.2% of patients, the FDA said in its summary of on the data supporting the application. This measure is known as sensitivity, meaning it shows how often an individual has the condition addressed in the test. 

Meanwhile, the false positive rate was 20.8%, the FDA said. 

SOLVD published similar study results in 2021. 

The company failed to impress the FDA’s Clinical Chemistry and Clinical Toxicology Devices Panel, which in October 2022, said the probable risks of the test likely outweighed its benefits. 

Then, in November 2022, the FDA and National Institutes of Health (NIH) held a public workshop meeting  to consider the challenges and possibilities in developing tools to predict the risk of developing OUD. At that meeting, Keri Donaldson, MD, MSCE, the chief executive officer of SOLVD, said the company planned to conduct a controlled rollout of AdvertD on FDA approval. 

Dr. Donaldson said a “defined set” of clinicians would first access the test, allowing the company to understand how results would be used in clinical practice.

“Once a test gets into practice, you have to be very purposeful and thoughtful about how it’s used,” he said.

The FDA approved the test in December 2023, saying it had worked with the company on modifications to its test. It also said that the advisory committee’s feedback helped in the evaluation and ultimate approval of AdvertD. 

Even beyond the debate about the predictive ability of genetic tests for OUD are larger questions that physicians need time to ask patients in assessing their potential risk for addiction when prescribing narcotic painkillers, said Maya Hambright, MD, a physician in New York’s Hudson Valley who has been working mainly in addiction in response to the overdose crisis. 

Genetics are just one of many factors at play in causing people to become addicted to opioids, Dr. Hambright said. 

Physicians must also consider the lasting effects of emotional and physical trauma experienced at any age, but particularly in childhood, as well as what kind of social support a patient has in facing the illness or injury that may require opioids for pain, she said. 

“There is a time and place for narcotic medications to be prescribed appropriately, which means we have to do our due diligence,” Dr. Hambright told this news organization. “Regardless of the strides we make in research and development, we still must connect and communicate safely and effectively and compassionately with our patients.” 

A version of this article appeared on Medscape.com.

A group of researchers urged US regulators to revoke the approval of a test marketed for predicting risk for opioid addiction and said government health plans should not pay for the product. 

The focus of the request is AdvertD (SOLVD Health), which the US Food and Drug Administration (FDA) approved in December as the first test to use DNA to evaluate if people have an elevated risk for opioid use disorder (OUD). A sample obtained through a cheek swab is meant to help guide decisions about opioid prescriptions for patients not previously treated with these drugs, such as someone undergoing a planned surgery, the FDA said. 

But Michael T. Abrams, MPH, PhD, senior health researcher for Public Citizen’s Health Research Group, and 30 other physicians and researchers sent an April 4 letter to the Food and Drug Administration calling on the government to reconsider. 

Dr. Abrams and fellow signers of the letters, including longtime opioid watchdog Andrew Kolodny, MD, of Brandeis University, said the algorithm used in creating AvertD “fell into known pitfalls of genetic prediction that give the appearance of predicting genetic risk, without being a true measure of genetic risk.” 

“The harmful consequences of an invalid genetic test for OUD are clear. Patients who test negative, and their clinicians, may have a false sense of security about use of opioids,” the letter states. 

The letter adds that false-positive test results may result in harmful consequences, with clinicians refraining from prescribing needed opioids, a problem that may be magnified in minority populations. 

Among the signers of the letter is Alexander Hatoum, PhD, of Washington University, who conducted an independent evaluation of AdvertD, which he and his colleagues published in 2021 in Drug and Alcohol Dependency. 

Dr. Hatoum said many patients may not fully understand the limit of genetic testing in predicting conditions like risk for OUD, where many factors are at play. The availability of a test may lend the impression that a single DNA trait makes the difference, as happens with conditions like Huntington’s disease and cystic fibrosis, he said. 

“But it’s just not reality for most diseases,” Dr. Hatoum told this news organization. 

The FDA declined to comment on the letter and said its approval of the test was “another step forward” in efforts to prevent new cases of OUD. 

In 2021, a little more than three quarters of people who died by overdose in the United States involved opioids, or more than 80,000 people, according to the US Centers for Disease Control and Prevention. This figure includes prescription opioids, heroin, and fentanyl. 

While deaths from overdoses with prescription opioids peaked in 2017 at 17,029 people, that figure has decreased steadily. Meanwhile, synthetic opioids other than methadone — primarily fentanyl — were the main driver of drug overdose deaths with a nearly 7.5-fold increase from 2015 to 2021. 

The FDA agency said it had “a reasonable assurance of AvertD’s safety and effectiveness, taking into consideration available alternatives, patients’ perspectives, the public health need and the ability to address uncertainty through the collection of post-market data.” 

Slow Rollout

In a separate letter to the Centers for Medicare and Medicaid Services, Dr. Abrams, Dr. Kolodny, Dr. Hatoum, and the other signers repeated their arguments against the use of AdvertD and asked that the government not use federal funds to pay for the test. 

SOLVD is not yet selling AdvertD in the United States, and it has not yet set a price for the product. The Carlsbad, California-based company told this news organization in an email exchange that it is working with both Medicare and private insurers on questions of future coverage. 

AvertD correctly identified an elevated risk for OUD in about 82.8% of cases, equating to a false-negative rate of 18.2% of patients, the FDA said in its summary of on the data supporting the application. This measure is known as sensitivity, meaning it shows how often an individual has the condition addressed in the test. 

Meanwhile, the false positive rate was 20.8%, the FDA said. 

SOLVD published similar study results in 2021. 

The company failed to impress the FDA’s Clinical Chemistry and Clinical Toxicology Devices Panel, which in October 2022, said the probable risks of the test likely outweighed its benefits. 

Then, in November 2022, the FDA and National Institutes of Health (NIH) held a public workshop meeting  to consider the challenges and possibilities in developing tools to predict the risk of developing OUD. At that meeting, Keri Donaldson, MD, MSCE, the chief executive officer of SOLVD, said the company planned to conduct a controlled rollout of AdvertD on FDA approval. 

Dr. Donaldson said a “defined set” of clinicians would first access the test, allowing the company to understand how results would be used in clinical practice.

“Once a test gets into practice, you have to be very purposeful and thoughtful about how it’s used,” he said.

The FDA approved the test in December 2023, saying it had worked with the company on modifications to its test. It also said that the advisory committee’s feedback helped in the evaluation and ultimate approval of AdvertD. 

Even beyond the debate about the predictive ability of genetic tests for OUD are larger questions that physicians need time to ask patients in assessing their potential risk for addiction when prescribing narcotic painkillers, said Maya Hambright, MD, a physician in New York’s Hudson Valley who has been working mainly in addiction in response to the overdose crisis. 

Genetics are just one of many factors at play in causing people to become addicted to opioids, Dr. Hambright said. 

Physicians must also consider the lasting effects of emotional and physical trauma experienced at any age, but particularly in childhood, as well as what kind of social support a patient has in facing the illness or injury that may require opioids for pain, she said. 

“There is a time and place for narcotic medications to be prescribed appropriately, which means we have to do our due diligence,” Dr. Hambright told this news organization. “Regardless of the strides we make in research and development, we still must connect and communicate safely and effectively and compassionately with our patients.” 

A version of this article appeared on Medscape.com.

Immersive virtual reality (VR) distraction therapy may be more effective at controlling pain in hospitalized patients with cancer than a two-dimensional guided imagery experience, suggests a new randomized controlled trial.

While both interventions brought some pain relief, VR therapy yielded greater, longer-lasting comfort, reported lead author Hunter Groninger, MD, of MedStar Health Research Institute, Hyattsville, Maryland, and colleagues.

MedStar Health

“Investigators have explored immersive VR interventions in cancer populations for a variety of indications including anxiety, depression, fatigue, and procedure‐associated pain, particularly among patients with pediatric cancer and adult breast cancer,” the investigators wrote in Cancer. “Nevertheless, despite growing evidence supporting the efficacy of VR‐delivered interventions for analgesia, few data address its role to mitigate cancer‐related pain specifically.”

To address this knowledge gap, Dr. Groninger and colleagues enrolled 128 adult hospitalized patients with cancer of any kind, all of whom had moderate to severe pain (self-reported score at least 4 out of 10) within the past 24 hours.
 

Study Methods and Results

Patients were randomized to receive either 10 minutes of immersive VR distraction therapy or 10 minutes of two-dimensional guided imagery distraction therapy.

“[The VR therapy] provides noncompetitive experiences in which the user can move around and explore natural environments (e.g., beachscape, forest) from standing, seated, or fixed positions, including within a hospital bed or chair,” the investigators wrote. “We provided over‐the‐ear headphones to assure high sound quality for the experience in the virtual natural environment.”

The two-dimensional intervention, delivered via electronic tablet, featured a meditation with images of natural landscapes and instrumental background music.

“We chose this active control because it is readily available and reflects content similar to relaxation‐focused television channels that are increasingly common in hospital settings,” the investigators noted.

Compared with this more common approach, patients who received VR therapy had significantly greater immediate reduction in pain (mean change in pain score, –1.4 vs –0.7; P = .03). Twenty-four hours later, improvements in the VR group generally persisted, while pain level in the two-dimensional group returned almost to baseline (P = .004). In addition, patients in the VR group reported significantly greater improvements in general distress and pain bothersomeness.

“VR therapies may modulate the pain experience by reducing the level of attention paid to noxious stimuli, thereby suppressing transmission of painful sensations via pain processing pathways to the cerebral cortex, particularly with more active VR experiences compared to passive experiences,” the investigators wrote.
 

Downsides to Using VR

Although VR brought more benefit, participants in the VR group more often reported difficulty using the intervention compared with those who interacted with an electronic tablet.

Plus, one VR user described mild dizziness that resolved with pharmacologic intervention. Still, approximately 9 out of 10 participants in each group reported willingness to try the intervention again.
 

Future VR Research

“Virtual reality is a rapidly evolving technology with a wealth of potential patient‐facing applications,” the investigators wrote. “Future studies should explore repeated use, optimal dosing, and impact on VR therapy on opioid analgesic requirements as well as usability testing, VR content preferences and facilitators of analgesia, and barriers and facilitators to use in acute care settings.”

This study was supported by the American Cancer Society. The investigators disclosed no conflicts of interest.

Immersive virtual reality (VR) distraction therapy may be more effective at controlling pain in hospitalized patients with cancer than a two-dimensional guided imagery experience, suggests a new randomized controlled trial.

While both interventions brought some pain relief, VR therapy yielded greater, longer-lasting comfort, reported lead author Hunter Groninger, MD, of MedStar Health Research Institute, Hyattsville, Maryland, and colleagues.

MedStar Health

“Investigators have explored immersive VR interventions in cancer populations for a variety of indications including anxiety, depression, fatigue, and procedure‐associated pain, particularly among patients with pediatric cancer and adult breast cancer,” the investigators wrote in Cancer. “Nevertheless, despite growing evidence supporting the efficacy of VR‐delivered interventions for analgesia, few data address its role to mitigate cancer‐related pain specifically.”

To address this knowledge gap, Dr. Groninger and colleagues enrolled 128 adult hospitalized patients with cancer of any kind, all of whom had moderate to severe pain (self-reported score at least 4 out of 10) within the past 24 hours.
 

Study Methods and Results

Patients were randomized to receive either 10 minutes of immersive VR distraction therapy or 10 minutes of two-dimensional guided imagery distraction therapy.

“[The VR therapy] provides noncompetitive experiences in which the user can move around and explore natural environments (e.g., beachscape, forest) from standing, seated, or fixed positions, including within a hospital bed or chair,” the investigators wrote. “We provided over‐the‐ear headphones to assure high sound quality for the experience in the virtual natural environment.”

The two-dimensional intervention, delivered via electronic tablet, featured a meditation with images of natural landscapes and instrumental background music.

“We chose this active control because it is readily available and reflects content similar to relaxation‐focused television channels that are increasingly common in hospital settings,” the investigators noted.

Compared with this more common approach, patients who received VR therapy had significantly greater immediate reduction in pain (mean change in pain score, –1.4 vs –0.7; P = .03). Twenty-four hours later, improvements in the VR group generally persisted, while pain level in the two-dimensional group returned almost to baseline (P = .004). In addition, patients in the VR group reported significantly greater improvements in general distress and pain bothersomeness.

“VR therapies may modulate the pain experience by reducing the level of attention paid to noxious stimuli, thereby suppressing transmission of painful sensations via pain processing pathways to the cerebral cortex, particularly with more active VR experiences compared to passive experiences,” the investigators wrote.
 

Downsides to Using VR

Although VR brought more benefit, participants in the VR group more often reported difficulty using the intervention compared with those who interacted with an electronic tablet.

Plus, one VR user described mild dizziness that resolved with pharmacologic intervention. Still, approximately 9 out of 10 participants in each group reported willingness to try the intervention again.
 

Future VR Research

“Virtual reality is a rapidly evolving technology with a wealth of potential patient‐facing applications,” the investigators wrote. “Future studies should explore repeated use, optimal dosing, and impact on VR therapy on opioid analgesic requirements as well as usability testing, VR content preferences and facilitators of analgesia, and barriers and facilitators to use in acute care settings.”

This study was supported by the American Cancer Society. The investigators disclosed no conflicts of interest.

Immersive virtual reality (VR) distraction therapy may be more effective at controlling pain in hospitalized patients with cancer than a two-dimensional guided imagery experience, suggests a new randomized controlled trial.

While both interventions brought some pain relief, VR therapy yielded greater, longer-lasting comfort, reported lead author Hunter Groninger, MD, of MedStar Health Research Institute, Hyattsville, Maryland, and colleagues.

MedStar Health

“Investigators have explored immersive VR interventions in cancer populations for a variety of indications including anxiety, depression, fatigue, and procedure‐associated pain, particularly among patients with pediatric cancer and adult breast cancer,” the investigators wrote in Cancer. “Nevertheless, despite growing evidence supporting the efficacy of VR‐delivered interventions for analgesia, few data address its role to mitigate cancer‐related pain specifically.”

To address this knowledge gap, Dr. Groninger and colleagues enrolled 128 adult hospitalized patients with cancer of any kind, all of whom had moderate to severe pain (self-reported score at least 4 out of 10) within the past 24 hours.
 

Study Methods and Results

Patients were randomized to receive either 10 minutes of immersive VR distraction therapy or 10 minutes of two-dimensional guided imagery distraction therapy.

“[The VR therapy] provides noncompetitive experiences in which the user can move around and explore natural environments (e.g., beachscape, forest) from standing, seated, or fixed positions, including within a hospital bed or chair,” the investigators wrote. “We provided over‐the‐ear headphones to assure high sound quality for the experience in the virtual natural environment.”

The two-dimensional intervention, delivered via electronic tablet, featured a meditation with images of natural landscapes and instrumental background music.

“We chose this active control because it is readily available and reflects content similar to relaxation‐focused television channels that are increasingly common in hospital settings,” the investigators noted.

Compared with this more common approach, patients who received VR therapy had significantly greater immediate reduction in pain (mean change in pain score, –1.4 vs –0.7; P = .03). Twenty-four hours later, improvements in the VR group generally persisted, while pain level in the two-dimensional group returned almost to baseline (P = .004). In addition, patients in the VR group reported significantly greater improvements in general distress and pain bothersomeness.

“VR therapies may modulate the pain experience by reducing the level of attention paid to noxious stimuli, thereby suppressing transmission of painful sensations via pain processing pathways to the cerebral cortex, particularly with more active VR experiences compared to passive experiences,” the investigators wrote.
 

Downsides to Using VR

Although VR brought more benefit, participants in the VR group more often reported difficulty using the intervention compared with those who interacted with an electronic tablet.

Plus, one VR user described mild dizziness that resolved with pharmacologic intervention. Still, approximately 9 out of 10 participants in each group reported willingness to try the intervention again.
 

Future VR Research

“Virtual reality is a rapidly evolving technology with a wealth of potential patient‐facing applications,” the investigators wrote. “Future studies should explore repeated use, optimal dosing, and impact on VR therapy on opioid analgesic requirements as well as usability testing, VR content preferences and facilitators of analgesia, and barriers and facilitators to use in acute care settings.”

This study was supported by the American Cancer Society. The investigators disclosed no conflicts of interest.