Pain

Postoperative chronic pain (POCP) is common and is expected to become increasingly prevalent. This type of pain, however, which specifically arises following surgery, independent of any infection or surgical failure, remains poorly understood. Facilities dedicated to treating it are nearly nonexistent.

At the 2024 congress of the French Society of Anesthesia and Resuscitation, anesthesiologists specializing in pain management advocated for improved management of POCP. They put themselves forward as essential interlocutors and actors in this effort. The anesthesiologists also called for better recognition of postoperative pain by patients, general practitioners, and surgeons to enable early intervention and reduce the risk for chronicity.
 

Underrecognized, Poorly Managed

POCP is defined as persistent pain lasting more than 3 months after surgery, unrelated to preoperative pain, and not associated with surgical complications. It can manifest in various forms, but the most typical scenario involves a patient complaining of persistent pain that developed following a surgical procedure. Normal radiological and biologic assessments rule out infectious complications. The persistence of pain long after surgery contrasts with what is often considered a successful surgical outcome by the surgeon.

“Of the 10 million patients operated on each year in France, it is estimated that about 10% will develop POCP, equating to 1.2 million patients,” explained Cyril Quémeneur, a specialist in anesthesiology and pain management at Pitié-Salpêtrière Hospital in Paris, France.

Because of the increasing number of surgical interventions in recent years, POCP has become a major concern. “Currently, there are 275 facilities dedicated to chronic pain across the country, capable of accommodating between 300,000 and 400,000 patients. Given that knee replacement surgery — the incidence of which is rising sharply — results in postoperative pain for 20%-30% of operated patients, the question of managing this type of pain will become even more pressing in the future,” said Quémeneur.

Moreover, specialized facilities for transitional pain management are not widespread in France, unlike in Canada, which has been developing them for about a decade, he noted.

France’s pain treatment centers “are overwhelmed,” said Gilles Lebuffe, a specialist in anesthesiology and pain management at Lille University Hospital in Lille, France. “Thus, the time between when the patient is operated on and when we discuss chronic pain allows the painful condition to establish itself, leading to central sensitization at the neurological level.” Once established, this pain is difficult to treat. “The later a patient arrives at a pain center, the more challenging the situation is to manage,” said Lebuffe.
 

Risk Factors

It is therefore crucial to identify patients at higher risk for postoperative pain during the anesthesia consultation, thus allowing for monitoring during the postoperative period. These pains can be highly debilitating because of their intensity, chronicity, and impact on quality of life.

To target these patients, it is essential to understand which surgeries and patient types constitute risk factors, as well as the characteristics of the pain experienced.

While all surgeries can lead to POCP, certain procedures are more likely to result in chronic pain. They include breast surgery with mastectomy, thoracic and spinal surgery, amputations, and knee replacement surgery. Notably, surgical repair of inguinal hernias, considered routine surgery, is emblematic of the risk for POCP. Its incidence after this procedure is 10% or more in the literature.

In addition, POCP often has neuropathic characteristics. Patients frequently describe their pain using terms like “burning” or “electric shock.” These pains are often associated with strange sensations such as tingling, prickling, itching, or numbness. “This describes neuropathic pain, which increases the risk of chronicity,” said Lebuffe.
 

Preoperative Opioid Use

Another warning sign for healthcare professionals is that patients with chronic pain may have factors associated with vulnerability. Women, who have a higher incidence of chronic pain syndrome, are at greater risk of developing postoperative chronic pain than men.

It has also been shown that preoperative opioid use leads to higher postoperative pain intensities for several days. This is a factor to consider, even though opioid consumption rates in France are far lower than those in the United States, where as much as 35% of patients use opioids preoperatively, said Frédéric Aubrun, head of the Anesthesia and Intensive Care Department and a pain management specialist at the Hospices Civils de Lyon in Lyon, France. Finally, significant literature indicates that psychological fragility is a risk factor for more intense acute pain and for POCP. “Patients with chronic pain frequently have depressive symptoms and anxiety,” said Lebuffe.
 

Involving General Practitioners

Because one responsibility of general practitioners is to identify patients with abnormal postoperative pain trajectories, the anesthesiologists at the press conference advocated for greater patient awareness and increased involvement of general practitioners in this identification process.

“If there is an expected duration of postoperative pain at varying intensities, since it all depends on the patient’s journey (the number of reoperations, history of opioid use, etc.), it is necessary to make patients aware that it is not normal to suffer long after a surgical intervention,” said Aubrun. In addition, it is important to “connect with primary care” and mobilize general practitioners to “detect patients sliding toward opioid overconsumption” and refer them to the appropriate care structure, he said.

Although dedicated facilities for this type of pain — like transitional pain clinics in Canada or northern Europe — do not exist in France, some hospitals, like Lille University Hospital, have established “intermediate consultations targeting patients with specific pain or chronicity characteristics. In these consultations, patients are systematically reviewed 4-6 weeks after surgery by the surgeon, who has been trained to identify neuropathic pain,” said Lebuffe. When a patient with such pain is identified, he or she is referred to an intermediate consultation and seen by a fellow anesthesiologist. The advantage of this consultation is that it is linked to a chronic pain structure. Consequently, frequent exchanges occur with the pain specialists involved in this structure, thus allowing for immediate optimization of pain treatments. The goal is to halt the process of central sensitization.

“We strongly believe in this type of transitional structure, even though it requires significant human resources,” said Lebuffe. He also called for a “societal reflection” on this issue because patients with chronic pain represent a significant cost to society, in terms of medications and work stoppages. Moreover, patients who are forced to stop working see their lives disrupted.
 

Managing POCP

When POCP with neuropathic characteristics has been diagnosed, specific treatments and techniques for chronic pain can be prescribed earlier than they currently are. “Systemic drug treatments for neuropathic POCP rely on various therapeutic classes (opioids, antidepressants, antiepileptics), which are not without side effects for the patient,” said Violaine D’ans, an anesthesiologist and pain management specialist at Polyclinique du Parc in Caen, France. Hence, the idea is to prescribe a minimal dose while providing the patient with techniques available to anesthesiologists. “We have a good range of management options that we use in perioperative pain management, and we have a role to play in radio- or CT-guided perinerve infiltrations, with continuous peripheral nerve blocks and possibly later with electrostimulation to help restore movement and avoid kinesiophobia.”

This story was translated from the Medscape French edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Postoperative chronic pain (POCP) is common and is expected to become increasingly prevalent. This type of pain, however, which specifically arises following surgery, independent of any infection or surgical failure, remains poorly understood. Facilities dedicated to treating it are nearly nonexistent.

At the 2024 congress of the French Society of Anesthesia and Resuscitation, anesthesiologists specializing in pain management advocated for improved management of POCP. They put themselves forward as essential interlocutors and actors in this effort. The anesthesiologists also called for better recognition of postoperative pain by patients, general practitioners, and surgeons to enable early intervention and reduce the risk for chronicity.
 

Underrecognized, Poorly Managed

POCP is defined as persistent pain lasting more than 3 months after surgery, unrelated to preoperative pain, and not associated with surgical complications. It can manifest in various forms, but the most typical scenario involves a patient complaining of persistent pain that developed following a surgical procedure. Normal radiological and biologic assessments rule out infectious complications. The persistence of pain long after surgery contrasts with what is often considered a successful surgical outcome by the surgeon.

“Of the 10 million patients operated on each year in France, it is estimated that about 10% will develop POCP, equating to 1.2 million patients,” explained Cyril Quémeneur, a specialist in anesthesiology and pain management at Pitié-Salpêtrière Hospital in Paris, France.

Because of the increasing number of surgical interventions in recent years, POCP has become a major concern. “Currently, there are 275 facilities dedicated to chronic pain across the country, capable of accommodating between 300,000 and 400,000 patients. Given that knee replacement surgery — the incidence of which is rising sharply — results in postoperative pain for 20%-30% of operated patients, the question of managing this type of pain will become even more pressing in the future,” said Quémeneur.

Moreover, specialized facilities for transitional pain management are not widespread in France, unlike in Canada, which has been developing them for about a decade, he noted.

France’s pain treatment centers “are overwhelmed,” said Gilles Lebuffe, a specialist in anesthesiology and pain management at Lille University Hospital in Lille, France. “Thus, the time between when the patient is operated on and when we discuss chronic pain allows the painful condition to establish itself, leading to central sensitization at the neurological level.” Once established, this pain is difficult to treat. “The later a patient arrives at a pain center, the more challenging the situation is to manage,” said Lebuffe.
 

Risk Factors

It is therefore crucial to identify patients at higher risk for postoperative pain during the anesthesia consultation, thus allowing for monitoring during the postoperative period. These pains can be highly debilitating because of their intensity, chronicity, and impact on quality of life.

To target these patients, it is essential to understand which surgeries and patient types constitute risk factors, as well as the characteristics of the pain experienced.

While all surgeries can lead to POCP, certain procedures are more likely to result in chronic pain. They include breast surgery with mastectomy, thoracic and spinal surgery, amputations, and knee replacement surgery. Notably, surgical repair of inguinal hernias, considered routine surgery, is emblematic of the risk for POCP. Its incidence after this procedure is 10% or more in the literature.

In addition, POCP often has neuropathic characteristics. Patients frequently describe their pain using terms like “burning” or “electric shock.” These pains are often associated with strange sensations such as tingling, prickling, itching, or numbness. “This describes neuropathic pain, which increases the risk of chronicity,” said Lebuffe.
 

Preoperative Opioid Use

Another warning sign for healthcare professionals is that patients with chronic pain may have factors associated with vulnerability. Women, who have a higher incidence of chronic pain syndrome, are at greater risk of developing postoperative chronic pain than men.

It has also been shown that preoperative opioid use leads to higher postoperative pain intensities for several days. This is a factor to consider, even though opioid consumption rates in France are far lower than those in the United States, where as much as 35% of patients use opioids preoperatively, said Frédéric Aubrun, head of the Anesthesia and Intensive Care Department and a pain management specialist at the Hospices Civils de Lyon in Lyon, France. Finally, significant literature indicates that psychological fragility is a risk factor for more intense acute pain and for POCP. “Patients with chronic pain frequently have depressive symptoms and anxiety,” said Lebuffe.
 

Involving General Practitioners

Because one responsibility of general practitioners is to identify patients with abnormal postoperative pain trajectories, the anesthesiologists at the press conference advocated for greater patient awareness and increased involvement of general practitioners in this identification process.

“If there is an expected duration of postoperative pain at varying intensities, since it all depends on the patient’s journey (the number of reoperations, history of opioid use, etc.), it is necessary to make patients aware that it is not normal to suffer long after a surgical intervention,” said Aubrun. In addition, it is important to “connect with primary care” and mobilize general practitioners to “detect patients sliding toward opioid overconsumption” and refer them to the appropriate care structure, he said.

Although dedicated facilities for this type of pain — like transitional pain clinics in Canada or northern Europe — do not exist in France, some hospitals, like Lille University Hospital, have established “intermediate consultations targeting patients with specific pain or chronicity characteristics. In these consultations, patients are systematically reviewed 4-6 weeks after surgery by the surgeon, who has been trained to identify neuropathic pain,” said Lebuffe. When a patient with such pain is identified, he or she is referred to an intermediate consultation and seen by a fellow anesthesiologist. The advantage of this consultation is that it is linked to a chronic pain structure. Consequently, frequent exchanges occur with the pain specialists involved in this structure, thus allowing for immediate optimization of pain treatments. The goal is to halt the process of central sensitization.

“We strongly believe in this type of transitional structure, even though it requires significant human resources,” said Lebuffe. He also called for a “societal reflection” on this issue because patients with chronic pain represent a significant cost to society, in terms of medications and work stoppages. Moreover, patients who are forced to stop working see their lives disrupted.
 

Managing POCP

When POCP with neuropathic characteristics has been diagnosed, specific treatments and techniques for chronic pain can be prescribed earlier than they currently are. “Systemic drug treatments for neuropathic POCP rely on various therapeutic classes (opioids, antidepressants, antiepileptics), which are not without side effects for the patient,” said Violaine D’ans, an anesthesiologist and pain management specialist at Polyclinique du Parc in Caen, France. Hence, the idea is to prescribe a minimal dose while providing the patient with techniques available to anesthesiologists. “We have a good range of management options that we use in perioperative pain management, and we have a role to play in radio- or CT-guided perinerve infiltrations, with continuous peripheral nerve blocks and possibly later with electrostimulation to help restore movement and avoid kinesiophobia.”

This story was translated from the Medscape French edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Postoperative chronic pain (POCP) is common and is expected to become increasingly prevalent. This type of pain, however, which specifically arises following surgery, independent of any infection or surgical failure, remains poorly understood. Facilities dedicated to treating it are nearly nonexistent.

At the 2024 congress of the French Society of Anesthesia and Resuscitation, anesthesiologists specializing in pain management advocated for improved management of POCP. They put themselves forward as essential interlocutors and actors in this effort. The anesthesiologists also called for better recognition of postoperative pain by patients, general practitioners, and surgeons to enable early intervention and reduce the risk for chronicity.
 

Underrecognized, Poorly Managed

POCP is defined as persistent pain lasting more than 3 months after surgery, unrelated to preoperative pain, and not associated with surgical complications. It can manifest in various forms, but the most typical scenario involves a patient complaining of persistent pain that developed following a surgical procedure. Normal radiological and biologic assessments rule out infectious complications. The persistence of pain long after surgery contrasts with what is often considered a successful surgical outcome by the surgeon.

“Of the 10 million patients operated on each year in France, it is estimated that about 10% will develop POCP, equating to 1.2 million patients,” explained Cyril Quémeneur, a specialist in anesthesiology and pain management at Pitié-Salpêtrière Hospital in Paris, France.

Because of the increasing number of surgical interventions in recent years, POCP has become a major concern. “Currently, there are 275 facilities dedicated to chronic pain across the country, capable of accommodating between 300,000 and 400,000 patients. Given that knee replacement surgery — the incidence of which is rising sharply — results in postoperative pain for 20%-30% of operated patients, the question of managing this type of pain will become even more pressing in the future,” said Quémeneur.

Moreover, specialized facilities for transitional pain management are not widespread in France, unlike in Canada, which has been developing them for about a decade, he noted.

France’s pain treatment centers “are overwhelmed,” said Gilles Lebuffe, a specialist in anesthesiology and pain management at Lille University Hospital in Lille, France. “Thus, the time between when the patient is operated on and when we discuss chronic pain allows the painful condition to establish itself, leading to central sensitization at the neurological level.” Once established, this pain is difficult to treat. “The later a patient arrives at a pain center, the more challenging the situation is to manage,” said Lebuffe.
 

Risk Factors

It is therefore crucial to identify patients at higher risk for postoperative pain during the anesthesia consultation, thus allowing for monitoring during the postoperative period. These pains can be highly debilitating because of their intensity, chronicity, and impact on quality of life.

To target these patients, it is essential to understand which surgeries and patient types constitute risk factors, as well as the characteristics of the pain experienced.

While all surgeries can lead to POCP, certain procedures are more likely to result in chronic pain. They include breast surgery with mastectomy, thoracic and spinal surgery, amputations, and knee replacement surgery. Notably, surgical repair of inguinal hernias, considered routine surgery, is emblematic of the risk for POCP. Its incidence after this procedure is 10% or more in the literature.

In addition, POCP often has neuropathic characteristics. Patients frequently describe their pain using terms like “burning” or “electric shock.” These pains are often associated with strange sensations such as tingling, prickling, itching, or numbness. “This describes neuropathic pain, which increases the risk of chronicity,” said Lebuffe.
 

Preoperative Opioid Use

Another warning sign for healthcare professionals is that patients with chronic pain may have factors associated with vulnerability. Women, who have a higher incidence of chronic pain syndrome, are at greater risk of developing postoperative chronic pain than men.

It has also been shown that preoperative opioid use leads to higher postoperative pain intensities for several days. This is a factor to consider, even though opioid consumption rates in France are far lower than those in the United States, where as much as 35% of patients use opioids preoperatively, said Frédéric Aubrun, head of the Anesthesia and Intensive Care Department and a pain management specialist at the Hospices Civils de Lyon in Lyon, France. Finally, significant literature indicates that psychological fragility is a risk factor for more intense acute pain and for POCP. “Patients with chronic pain frequently have depressive symptoms and anxiety,” said Lebuffe.
 

Involving General Practitioners

Because one responsibility of general practitioners is to identify patients with abnormal postoperative pain trajectories, the anesthesiologists at the press conference advocated for greater patient awareness and increased involvement of general practitioners in this identification process.

“If there is an expected duration of postoperative pain at varying intensities, since it all depends on the patient’s journey (the number of reoperations, history of opioid use, etc.), it is necessary to make patients aware that it is not normal to suffer long after a surgical intervention,” said Aubrun. In addition, it is important to “connect with primary care” and mobilize general practitioners to “detect patients sliding toward opioid overconsumption” and refer them to the appropriate care structure, he said.

Although dedicated facilities for this type of pain — like transitional pain clinics in Canada or northern Europe — do not exist in France, some hospitals, like Lille University Hospital, have established “intermediate consultations targeting patients with specific pain or chronicity characteristics. In these consultations, patients are systematically reviewed 4-6 weeks after surgery by the surgeon, who has been trained to identify neuropathic pain,” said Lebuffe. When a patient with such pain is identified, he or she is referred to an intermediate consultation and seen by a fellow anesthesiologist. The advantage of this consultation is that it is linked to a chronic pain structure. Consequently, frequent exchanges occur with the pain specialists involved in this structure, thus allowing for immediate optimization of pain treatments. The goal is to halt the process of central sensitization.

“We strongly believe in this type of transitional structure, even though it requires significant human resources,” said Lebuffe. He also called for a “societal reflection” on this issue because patients with chronic pain represent a significant cost to society, in terms of medications and work stoppages. Moreover, patients who are forced to stop working see their lives disrupted.
 

Managing POCP

When POCP with neuropathic characteristics has been diagnosed, specific treatments and techniques for chronic pain can be prescribed earlier than they currently are. “Systemic drug treatments for neuropathic POCP rely on various therapeutic classes (opioids, antidepressants, antiepileptics), which are not without side effects for the patient,” said Violaine D’ans, an anesthesiologist and pain management specialist at Polyclinique du Parc in Caen, France. Hence, the idea is to prescribe a minimal dose while providing the patient with techniques available to anesthesiologists. “We have a good range of management options that we use in perioperative pain management, and we have a role to play in radio- or CT-guided perinerve infiltrations, with continuous peripheral nerve blocks and possibly later with electrostimulation to help restore movement and avoid kinesiophobia.”

This story was translated from the Medscape French edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

As at-home, do-it-yourself (DIY) brain stimulation devices like transcranial direct current stimulation (tDCS) gain popularity for common psychiatric conditions like depression, anxiety, and posttraumatic stress disorder (PTSD), questions arise about their safety and efficacy.

However, the US Food and Drug Administration (FDA) has yet to “fully” clear any of these devices and has only granted breakthrough device designation to a few. In addition, most of the portable products don’t market themselves as medical interventions, putting them into a regulatory “gray area” that has little oversight.

This has led to a free-for-all environment, allowing individuals to purchase these products online and self-administer “treatment” — often without the guidance or even knowledge of their healthcare providers.

So how effective and safe are these noninvasive brain stimulators, and what guidance, if any, should clinicians provide to patients who are or are contemplating using them at home; what does the research show, and what are the ethical considerations?
 

What the Research Shows

Data from studies examining unsupervised at-home and use under medical supervision are mixed. Results from a recent randomized trial of more than 200 participants showed no significant difference in safety or efficacy between adjunctive at-home tDCS and at-home sham tDCS for depressive symptoms.

“To be fair, they did not find any unexpected safety issues. What they did find was that there was no clear signal that it worked,” said Noah S. Philip, MD, professor of psychiatry and human behavior, Warren Alpert Medical School of Brown University, Providence, Rhode Island.

Philip, who is also lead for mental health research at Brown’s Center for Neurorestoration and Neurotechnology, Providence, Rhode Island, and was not involved in the study, noted that while other research papers have shown more promising results for depression and other conditions such as adult attention-deficit/hyperactivity disorder (ADHD) and pain, they often are not placebo controlled or include large numbers of patients.

Still, he added the growing use of these devices reflects the fact that standard treatment often doesn’t meet patients’ needs.

“Broadly speaking, part of the hope with brain stimulation is that instead of taking a pill, we’re trying to more directly affect the brain tissues involved — and therefore, avoid the issue of having systemic side effects that you get from the meds. There’s certainly a hunger” for better interventions, Philip said.

tDCS involves a low-intensity electrical current applied through electrodes on the scalp in order to influence brain activity. Generally speaking, it emits less energy than other types of noninvasive brain stimulation, such as transcranial magnetic stimulation. “The trade-off is that’s it also a little harder to find a clear signal about how it works,” Philip said.

As such, he added, it’s important for clinicians to familiarize themselves with these devices, to ask about patient use, and to set up structured assessments of efficacy and adverse events.

Results from a randomized trial published last year in The Lancet showed no significant benefit for in-office use of tDCS plus a selective serotonin reuptake inhibitor vs sham tDCS for major depression.

On the other hand, a randomized trial published earlier this year in Brain Stimulation showed that older adults who received active tDCS had greater reductions in depressive and anxiety symptoms than those in the sham group.

In addition, results from a small study of eight participants published last year in SAGE Open Medicine showed adjuvant tDCS helped patients with refractory PTSD. Finally, a randomized trial of 54 veterans from Philip’s own team showed tDCS plus virtual reality was effective for combat-related PTSD.

Although there have also been several studies showing possible benefit of tDCS for Alzheimer’s disease, Gayatri Devi, MD, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York, noted in a Medscape Neurology Decision Point that “the problem with all these studies is that they’re all very small, and there [are] so many different variables in terms of how you interpret response.”
 

On-Demand Brain Stim

As for at-home use, there’s now a wide offering of these types of devices available online, allowing an individual to apply daily brain stimulation via headsets, dispensing with the need to consult a clinician. Most are battery-powered and emit a low-level current.

Philip noted that there are essentially two ways to obtain such devices. Some are readily available from online stores, while others require a prescription, which typically includes guidelines on how to use the device.

So far, none of these portable products have been fully cleared by the FDA — although the agency did grant Breakthrough Device designation to Sooma Medical for its device to treat depression in 2023 and to Flow Neuroscience in 2022.

In August 2023, Flow announced that its device is now being reviewed for full FDA clearance on the basis of trial results showing at-home tDCS was “twice as effective” as antidepressants. The company received regulatory approval in Europe in 2019.

Other research has shown “encouraging” results for these at-home devices for conditions such as adult ADHD and pain relief with remote supervision.

Philip noted that more high-quality randomized controlled trials are definitely needed, with “a number of companies probably getting close to releasing data sometime soon.”

Is it possible that a placebo effect is at work here? “Yes, partially,” said Philip. Users often become more mindful of managing their depression and other conditions, which leads to behavior change, he said.
 

A Quick Fix for a Broken System?

Joseph J. Fins, MD, The E. William Davis Jr, MD, professor of Medical Ethics and chief of the Division of Medical Ethics at Weill Cornell Medicine, New York City, also believes there could be a placebo effect at play.

“It’s important that we don’t ascribe efficacy to a device without being aware of the placebo effect,” he said. That’s why more and larger, placebo-controlled trials are needed, he added.

There’s a multitude of reasons why patients may turn to at-home devices on their own, including drug shortages and the inability to see a psychiatrist in a timely manner.

“I think it speaks to the isolation of these folks that leads to them doing this on their own. These devices become a technological quick fix for a system that’s desperately broken. There’s nothing wrong with being a consumer, but at a certain point they need to be a patient, and they need to have a clinician there to help them,” he said.

Fins said that he also worries about regulatory oversight because of the way the devices are classified. He likened them to supplements, which, because they don’t make certain claims, are not regulated with the same stringency as other products and fall into an area “in between regulatory spheres.”

“I think we’re trying to take old regulatory frameworks and jerry-rig it to accommodate new and evolving technologies. And I think we need to have serious study of how we protect patients as they become consumers — to make sure there’s enough safety and enough efficacy and that they don’t get ripped off out of desperation,” Fins said.

As for safety, at-home devices are unlikely to cause physical harm — at least when used as intended. “The riskier situations happen when people build their own, overuse it, or use it in combination with drugs or alcohol or other factors that can produce unpredictable results,” Philip said.

He added that DIY-built products carry a higher risk for burns or excessive energy output. A 2016 “open letter” from a group of neurologists, published in Annals of Neurology, warned about the dangers of DIY tDCS.

In addition, Philip noted that he has seen instances where patients become manic after using at-home tDCS, especially when trying to improve cognition.

“We have seen a number of peculiar side effects emerge in those situations. Typically, it’s anxiety, panic attacks, and sensitivity to bright lights, in addition to the emergence of mania, which would require major psychiatric intervention,” he said.

“So, it’s important that if folks do engage with these sorts of things, it’s with some degree of medical involvement,” Philip added.
 

Ethical Considerations

Roy Hamilton, MD, professor of neurology, psychiatry, and physical medicine & rehabilitation at the University of Pennsylvania, in Philadelphia, said that in the setting of proper training, proper clinician communication, and proper oversight, he doesn’t view at-home tDCS as ethically problematic.

“For individuals who have conditions that are clearly causing them remarkable detriment to quality of life or to their health, it seems like the risk-benefit ratio with respect to the likelihood of harm is quite good,” said Hamilton, who is also the director of the Penn Brain Science, Translation, Innovation, and Modulation Center.

In addition, tDCS and other transcranial electrical stimulation techniques seem to have a better safety profile than “many of the other things we send patients home with to treat their pain,” he said.

On the other hand, this risk calculus changes in a scenario where patients are neurologically intact, he said.

The brain, Hamilton noted, exhibits functional differences based on the region undergoing stimulation. This means users should follow a specific, prescribed method. However, he pointed out that those using commercially available devices often lack clear guidance on where to place the electrodes and what intensity to use.

“This raises concerns because the way you use the device is important,” he said.

Hamilton also highlighted important ethical considerations regarding enhanced cognition through technology or pharmaceutical interventions. The possibility of coercive use raises questions about equity and fairness, particularly if individuals feel pressured to use such devices to remain competitive in academic or professional settings.

This mirrors the current issues surrounding the use of stimulants among students, where those without ADHD may feel compelled to use these drugs to improve performance. In addition, there is the possibility that the capacity to access devices that enhance cognition could exacerbate existing inequalities.

“Any time you introduce a technological intervention, you have to worry about discriminative justice. That’s where only people who can afford such devices or have access to specialists who can give them such devices get to receive improvements in their cognition,” Hamilton said.

Neither the American Academy of Neurology nor the American Psychiatric Association has established practice guidelines for tDCS, either for use in clinical settings or for use at home. Hamilton believes this is due to the current lack of data, noting that organizations likely want to see more approvals and widespread use before creating guidelines.

Fins emphasized the need for organized medicine to sponsor research, noting that the use of these devices is becoming a public health issue. He expressed concern that some devices are marketed as nonmedical interventions, despite involving medical procedures like brain stimulation. He concluded that while scrutiny is necessary, the current landscape should be approached without judgment.

Fins reported no relevant financial relationships. Philip reported serving on a scientific advisory board for Pulvinar Neuro and past involvement in clinical trials related to these devices and their use as home. Hamilton reported he is on the board of trustees for the McKnight Brain Research Foundation, which is dedicated to advancing healthy cognitive aging.
 

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

As at-home, do-it-yourself (DIY) brain stimulation devices like transcranial direct current stimulation (tDCS) gain popularity for common psychiatric conditions like depression, anxiety, and posttraumatic stress disorder (PTSD), questions arise about their safety and efficacy.

However, the US Food and Drug Administration (FDA) has yet to “fully” clear any of these devices and has only granted breakthrough device designation to a few. In addition, most of the portable products don’t market themselves as medical interventions, putting them into a regulatory “gray area” that has little oversight.

This has led to a free-for-all environment, allowing individuals to purchase these products online and self-administer “treatment” — often without the guidance or even knowledge of their healthcare providers.

So how effective and safe are these noninvasive brain stimulators, and what guidance, if any, should clinicians provide to patients who are or are contemplating using them at home; what does the research show, and what are the ethical considerations?
 

What the Research Shows

Data from studies examining unsupervised at-home and use under medical supervision are mixed. Results from a recent randomized trial of more than 200 participants showed no significant difference in safety or efficacy between adjunctive at-home tDCS and at-home sham tDCS for depressive symptoms.

“To be fair, they did not find any unexpected safety issues. What they did find was that there was no clear signal that it worked,” said Noah S. Philip, MD, professor of psychiatry and human behavior, Warren Alpert Medical School of Brown University, Providence, Rhode Island.

Philip, who is also lead for mental health research at Brown’s Center for Neurorestoration and Neurotechnology, Providence, Rhode Island, and was not involved in the study, noted that while other research papers have shown more promising results for depression and other conditions such as adult attention-deficit/hyperactivity disorder (ADHD) and pain, they often are not placebo controlled or include large numbers of patients.

Still, he added the growing use of these devices reflects the fact that standard treatment often doesn’t meet patients’ needs.

“Broadly speaking, part of the hope with brain stimulation is that instead of taking a pill, we’re trying to more directly affect the brain tissues involved — and therefore, avoid the issue of having systemic side effects that you get from the meds. There’s certainly a hunger” for better interventions, Philip said.

tDCS involves a low-intensity electrical current applied through electrodes on the scalp in order to influence brain activity. Generally speaking, it emits less energy than other types of noninvasive brain stimulation, such as transcranial magnetic stimulation. “The trade-off is that’s it also a little harder to find a clear signal about how it works,” Philip said.

As such, he added, it’s important for clinicians to familiarize themselves with these devices, to ask about patient use, and to set up structured assessments of efficacy and adverse events.

Results from a randomized trial published last year in The Lancet showed no significant benefit for in-office use of tDCS plus a selective serotonin reuptake inhibitor vs sham tDCS for major depression.

On the other hand, a randomized trial published earlier this year in Brain Stimulation showed that older adults who received active tDCS had greater reductions in depressive and anxiety symptoms than those in the sham group.

In addition, results from a small study of eight participants published last year in SAGE Open Medicine showed adjuvant tDCS helped patients with refractory PTSD. Finally, a randomized trial of 54 veterans from Philip’s own team showed tDCS plus virtual reality was effective for combat-related PTSD.

Although there have also been several studies showing possible benefit of tDCS for Alzheimer’s disease, Gayatri Devi, MD, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York, noted in a Medscape Neurology Decision Point that “the problem with all these studies is that they’re all very small, and there [are] so many different variables in terms of how you interpret response.”
 

On-Demand Brain Stim

As for at-home use, there’s now a wide offering of these types of devices available online, allowing an individual to apply daily brain stimulation via headsets, dispensing with the need to consult a clinician. Most are battery-powered and emit a low-level current.

Philip noted that there are essentially two ways to obtain such devices. Some are readily available from online stores, while others require a prescription, which typically includes guidelines on how to use the device.

So far, none of these portable products have been fully cleared by the FDA — although the agency did grant Breakthrough Device designation to Sooma Medical for its device to treat depression in 2023 and to Flow Neuroscience in 2022.

In August 2023, Flow announced that its device is now being reviewed for full FDA clearance on the basis of trial results showing at-home tDCS was “twice as effective” as antidepressants. The company received regulatory approval in Europe in 2019.

Other research has shown “encouraging” results for these at-home devices for conditions such as adult ADHD and pain relief with remote supervision.

Philip noted that more high-quality randomized controlled trials are definitely needed, with “a number of companies probably getting close to releasing data sometime soon.”

Is it possible that a placebo effect is at work here? “Yes, partially,” said Philip. Users often become more mindful of managing their depression and other conditions, which leads to behavior change, he said.
 

A Quick Fix for a Broken System?

Joseph J. Fins, MD, The E. William Davis Jr, MD, professor of Medical Ethics and chief of the Division of Medical Ethics at Weill Cornell Medicine, New York City, also believes there could be a placebo effect at play.

“It’s important that we don’t ascribe efficacy to a device without being aware of the placebo effect,” he said. That’s why more and larger, placebo-controlled trials are needed, he added.

There’s a multitude of reasons why patients may turn to at-home devices on their own, including drug shortages and the inability to see a psychiatrist in a timely manner.

“I think it speaks to the isolation of these folks that leads to them doing this on their own. These devices become a technological quick fix for a system that’s desperately broken. There’s nothing wrong with being a consumer, but at a certain point they need to be a patient, and they need to have a clinician there to help them,” he said.

Fins said that he also worries about regulatory oversight because of the way the devices are classified. He likened them to supplements, which, because they don’t make certain claims, are not regulated with the same stringency as other products and fall into an area “in between regulatory spheres.”

“I think we’re trying to take old regulatory frameworks and jerry-rig it to accommodate new and evolving technologies. And I think we need to have serious study of how we protect patients as they become consumers — to make sure there’s enough safety and enough efficacy and that they don’t get ripped off out of desperation,” Fins said.

As for safety, at-home devices are unlikely to cause physical harm — at least when used as intended. “The riskier situations happen when people build their own, overuse it, or use it in combination with drugs or alcohol or other factors that can produce unpredictable results,” Philip said.

He added that DIY-built products carry a higher risk for burns or excessive energy output. A 2016 “open letter” from a group of neurologists, published in Annals of Neurology, warned about the dangers of DIY tDCS.

In addition, Philip noted that he has seen instances where patients become manic after using at-home tDCS, especially when trying to improve cognition.

“We have seen a number of peculiar side effects emerge in those situations. Typically, it’s anxiety, panic attacks, and sensitivity to bright lights, in addition to the emergence of mania, which would require major psychiatric intervention,” he said.

“So, it’s important that if folks do engage with these sorts of things, it’s with some degree of medical involvement,” Philip added.
 

Ethical Considerations

Roy Hamilton, MD, professor of neurology, psychiatry, and physical medicine & rehabilitation at the University of Pennsylvania, in Philadelphia, said that in the setting of proper training, proper clinician communication, and proper oversight, he doesn’t view at-home tDCS as ethically problematic.

“For individuals who have conditions that are clearly causing them remarkable detriment to quality of life or to their health, it seems like the risk-benefit ratio with respect to the likelihood of harm is quite good,” said Hamilton, who is also the director of the Penn Brain Science, Translation, Innovation, and Modulation Center.

In addition, tDCS and other transcranial electrical stimulation techniques seem to have a better safety profile than “many of the other things we send patients home with to treat their pain,” he said.

On the other hand, this risk calculus changes in a scenario where patients are neurologically intact, he said.

The brain, Hamilton noted, exhibits functional differences based on the region undergoing stimulation. This means users should follow a specific, prescribed method. However, he pointed out that those using commercially available devices often lack clear guidance on where to place the electrodes and what intensity to use.

“This raises concerns because the way you use the device is important,” he said.

Hamilton also highlighted important ethical considerations regarding enhanced cognition through technology or pharmaceutical interventions. The possibility of coercive use raises questions about equity and fairness, particularly if individuals feel pressured to use such devices to remain competitive in academic or professional settings.

This mirrors the current issues surrounding the use of stimulants among students, where those without ADHD may feel compelled to use these drugs to improve performance. In addition, there is the possibility that the capacity to access devices that enhance cognition could exacerbate existing inequalities.

“Any time you introduce a technological intervention, you have to worry about discriminative justice. That’s where only people who can afford such devices or have access to specialists who can give them such devices get to receive improvements in their cognition,” Hamilton said.

Neither the American Academy of Neurology nor the American Psychiatric Association has established practice guidelines for tDCS, either for use in clinical settings or for use at home. Hamilton believes this is due to the current lack of data, noting that organizations likely want to see more approvals and widespread use before creating guidelines.

Fins emphasized the need for organized medicine to sponsor research, noting that the use of these devices is becoming a public health issue. He expressed concern that some devices are marketed as nonmedical interventions, despite involving medical procedures like brain stimulation. He concluded that while scrutiny is necessary, the current landscape should be approached without judgment.

Fins reported no relevant financial relationships. Philip reported serving on a scientific advisory board for Pulvinar Neuro and past involvement in clinical trials related to these devices and their use as home. Hamilton reported he is on the board of trustees for the McKnight Brain Research Foundation, which is dedicated to advancing healthy cognitive aging.
 

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

As at-home, do-it-yourself (DIY) brain stimulation devices like transcranial direct current stimulation (tDCS) gain popularity for common psychiatric conditions like depression, anxiety, and posttraumatic stress disorder (PTSD), questions arise about their safety and efficacy.

However, the US Food and Drug Administration (FDA) has yet to “fully” clear any of these devices and has only granted breakthrough device designation to a few. In addition, most of the portable products don’t market themselves as medical interventions, putting them into a regulatory “gray area” that has little oversight.

This has led to a free-for-all environment, allowing individuals to purchase these products online and self-administer “treatment” — often without the guidance or even knowledge of their healthcare providers.

So how effective and safe are these noninvasive brain stimulators, and what guidance, if any, should clinicians provide to patients who are or are contemplating using them at home; what does the research show, and what are the ethical considerations?
 

What the Research Shows

Data from studies examining unsupervised at-home and use under medical supervision are mixed. Results from a recent randomized trial of more than 200 participants showed no significant difference in safety or efficacy between adjunctive at-home tDCS and at-home sham tDCS for depressive symptoms.

“To be fair, they did not find any unexpected safety issues. What they did find was that there was no clear signal that it worked,” said Noah S. Philip, MD, professor of psychiatry and human behavior, Warren Alpert Medical School of Brown University, Providence, Rhode Island.

Philip, who is also lead for mental health research at Brown’s Center for Neurorestoration and Neurotechnology, Providence, Rhode Island, and was not involved in the study, noted that while other research papers have shown more promising results for depression and other conditions such as adult attention-deficit/hyperactivity disorder (ADHD) and pain, they often are not placebo controlled or include large numbers of patients.

Still, he added the growing use of these devices reflects the fact that standard treatment often doesn’t meet patients’ needs.

“Broadly speaking, part of the hope with brain stimulation is that instead of taking a pill, we’re trying to more directly affect the brain tissues involved — and therefore, avoid the issue of having systemic side effects that you get from the meds. There’s certainly a hunger” for better interventions, Philip said.

tDCS involves a low-intensity electrical current applied through electrodes on the scalp in order to influence brain activity. Generally speaking, it emits less energy than other types of noninvasive brain stimulation, such as transcranial magnetic stimulation. “The trade-off is that’s it also a little harder to find a clear signal about how it works,” Philip said.

As such, he added, it’s important for clinicians to familiarize themselves with these devices, to ask about patient use, and to set up structured assessments of efficacy and adverse events.

Results from a randomized trial published last year in The Lancet showed no significant benefit for in-office use of tDCS plus a selective serotonin reuptake inhibitor vs sham tDCS for major depression.

On the other hand, a randomized trial published earlier this year in Brain Stimulation showed that older adults who received active tDCS had greater reductions in depressive and anxiety symptoms than those in the sham group.

In addition, results from a small study of eight participants published last year in SAGE Open Medicine showed adjuvant tDCS helped patients with refractory PTSD. Finally, a randomized trial of 54 veterans from Philip’s own team showed tDCS plus virtual reality was effective for combat-related PTSD.

Although there have also been several studies showing possible benefit of tDCS for Alzheimer’s disease, Gayatri Devi, MD, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York, noted in a Medscape Neurology Decision Point that “the problem with all these studies is that they’re all very small, and there [are] so many different variables in terms of how you interpret response.”
 

On-Demand Brain Stim

As for at-home use, there’s now a wide offering of these types of devices available online, allowing an individual to apply daily brain stimulation via headsets, dispensing with the need to consult a clinician. Most are battery-powered and emit a low-level current.

Philip noted that there are essentially two ways to obtain such devices. Some are readily available from online stores, while others require a prescription, which typically includes guidelines on how to use the device.

So far, none of these portable products have been fully cleared by the FDA — although the agency did grant Breakthrough Device designation to Sooma Medical for its device to treat depression in 2023 and to Flow Neuroscience in 2022.

In August 2023, Flow announced that its device is now being reviewed for full FDA clearance on the basis of trial results showing at-home tDCS was “twice as effective” as antidepressants. The company received regulatory approval in Europe in 2019.

Other research has shown “encouraging” results for these at-home devices for conditions such as adult ADHD and pain relief with remote supervision.

Philip noted that more high-quality randomized controlled trials are definitely needed, with “a number of companies probably getting close to releasing data sometime soon.”

Is it possible that a placebo effect is at work here? “Yes, partially,” said Philip. Users often become more mindful of managing their depression and other conditions, which leads to behavior change, he said.
 

A Quick Fix for a Broken System?

Joseph J. Fins, MD, The E. William Davis Jr, MD, professor of Medical Ethics and chief of the Division of Medical Ethics at Weill Cornell Medicine, New York City, also believes there could be a placebo effect at play.

“It’s important that we don’t ascribe efficacy to a device without being aware of the placebo effect,” he said. That’s why more and larger, placebo-controlled trials are needed, he added.

There’s a multitude of reasons why patients may turn to at-home devices on their own, including drug shortages and the inability to see a psychiatrist in a timely manner.

“I think it speaks to the isolation of these folks that leads to them doing this on their own. These devices become a technological quick fix for a system that’s desperately broken. There’s nothing wrong with being a consumer, but at a certain point they need to be a patient, and they need to have a clinician there to help them,” he said.

Fins said that he also worries about regulatory oversight because of the way the devices are classified. He likened them to supplements, which, because they don’t make certain claims, are not regulated with the same stringency as other products and fall into an area “in between regulatory spheres.”

“I think we’re trying to take old regulatory frameworks and jerry-rig it to accommodate new and evolving technologies. And I think we need to have serious study of how we protect patients as they become consumers — to make sure there’s enough safety and enough efficacy and that they don’t get ripped off out of desperation,” Fins said.

As for safety, at-home devices are unlikely to cause physical harm — at least when used as intended. “The riskier situations happen when people build their own, overuse it, or use it in combination with drugs or alcohol or other factors that can produce unpredictable results,” Philip said.

He added that DIY-built products carry a higher risk for burns or excessive energy output. A 2016 “open letter” from a group of neurologists, published in Annals of Neurology, warned about the dangers of DIY tDCS.

In addition, Philip noted that he has seen instances where patients become manic after using at-home tDCS, especially when trying to improve cognition.

“We have seen a number of peculiar side effects emerge in those situations. Typically, it’s anxiety, panic attacks, and sensitivity to bright lights, in addition to the emergence of mania, which would require major psychiatric intervention,” he said.

“So, it’s important that if folks do engage with these sorts of things, it’s with some degree of medical involvement,” Philip added.
 

Ethical Considerations

Roy Hamilton, MD, professor of neurology, psychiatry, and physical medicine & rehabilitation at the University of Pennsylvania, in Philadelphia, said that in the setting of proper training, proper clinician communication, and proper oversight, he doesn’t view at-home tDCS as ethically problematic.

“For individuals who have conditions that are clearly causing them remarkable detriment to quality of life or to their health, it seems like the risk-benefit ratio with respect to the likelihood of harm is quite good,” said Hamilton, who is also the director of the Penn Brain Science, Translation, Innovation, and Modulation Center.

In addition, tDCS and other transcranial electrical stimulation techniques seem to have a better safety profile than “many of the other things we send patients home with to treat their pain,” he said.

On the other hand, this risk calculus changes in a scenario where patients are neurologically intact, he said.

The brain, Hamilton noted, exhibits functional differences based on the region undergoing stimulation. This means users should follow a specific, prescribed method. However, he pointed out that those using commercially available devices often lack clear guidance on where to place the electrodes and what intensity to use.

“This raises concerns because the way you use the device is important,” he said.

Hamilton also highlighted important ethical considerations regarding enhanced cognition through technology or pharmaceutical interventions. The possibility of coercive use raises questions about equity and fairness, particularly if individuals feel pressured to use such devices to remain competitive in academic or professional settings.

This mirrors the current issues surrounding the use of stimulants among students, where those without ADHD may feel compelled to use these drugs to improve performance. In addition, there is the possibility that the capacity to access devices that enhance cognition could exacerbate existing inequalities.

“Any time you introduce a technological intervention, you have to worry about discriminative justice. That’s where only people who can afford such devices or have access to specialists who can give them such devices get to receive improvements in their cognition,” Hamilton said.

Neither the American Academy of Neurology nor the American Psychiatric Association has established practice guidelines for tDCS, either for use in clinical settings or for use at home. Hamilton believes this is due to the current lack of data, noting that organizations likely want to see more approvals and widespread use before creating guidelines.

Fins emphasized the need for organized medicine to sponsor research, noting that the use of these devices is becoming a public health issue. He expressed concern that some devices are marketed as nonmedical interventions, despite involving medical procedures like brain stimulation. He concluded that while scrutiny is necessary, the current landscape should be approached without judgment.

Fins reported no relevant financial relationships. Philip reported serving on a scientific advisory board for Pulvinar Neuro and past involvement in clinical trials related to these devices and their use as home. Hamilton reported he is on the board of trustees for the McKnight Brain Research Foundation, which is dedicated to advancing healthy cognitive aging.
 

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

Physicians who treat patients are potentially exposed to two opposing psychological processes: A positive feeling related to the experience of helping someone in need and, on the other hand, the adverse experience of seeing someone’s suffering and being frustrated about their inability to help. The ability to share the feelings of others is often referred to as empathy, while the ability to care for and show interest in others is the key aspect of compassion. Empathy makes it possible to share the positive and negative feelings of others in the same way: We can therefore feel happy when we indirectly share others’ joy and sad when we indirectly share others’ suffering.

Empathy in healthcare professionals is associated with patient satisfaction, diagnostic accuracy, adherence to treatment recommendations, clinical outcomes, clinical expertise, and physician retention. However, evidence indicates a tendency for empathy to decline during physicians’ training and specialization.
 

Estimating Empathy

Empathy studies are primarily based on observational data that include physician self-assessment or patient-perceived empathy. External evaluation of empathy by the recipient or observer is not the dominant approach, and a systematic review of the topic showed that, in 331 of the 470 studies examined (70.4%), individuals self-reported their level of empathy. The self-assessment system, particularly for doctors, is more likely to measure the doctor’s attitudes about empathy than empathy itself. The lack of correlation between physician and patient empathy assessments made it clear that patients cannot be disregarded when assessing physician empathy.

Consultation and Relational Empathy (CARE) is the primary assessment tool available to patients to measure physician empathy. It is a reliable and consistent system, particularly in primary care scenarios.

The CARE measure captures even small nuances of patient interactions with the physician and has been confirmed as a valuable tool in assessing the relational components of empathy.
 

Doctor-Patient Relationship

Communication with the physician is generally considered an important element of chronic pain care because it affects patient engagement and decision-making. A collaborative approach involving the patient and clinician in clinical decisions was associated with adherence to pain treatment and improved outcomes among patients with chronic lower back pain. The study conducted in a primary care setting of 1352 participants showed findings regarding physician empathy that did not necessarily involve a therapeutic alliance with the patient based on collaborative communication or expectation of a therapeutic effect of pharmacotherapy. Physician empathy remained the strongest factor associated with patient satisfaction, even after considering various potential confounders, including communication with the physician. In addition, ongoing empathy, especially when reported by patients with a long-term relationship with the physician, supported the hypothesis of a possible lasting effect on patient satisfaction.

Treating Chronic Pain

Empathy is an aspect of the doctor-patient relationship that may be particularly important in patients with chronic pain. A cohort study of 1470 patients with chronic low back pain analyzed whether and how it correlated with chronic pain outcomes. Patients reported their physician’s empathy at the time of enrollment using the CARE measure, which included 10 items on physician’s empathy characteristics during meetings. Physicians whose scores were 30 or higher (ie, rated as good, very good, or excellent in most items) were classified as very empathetic physicians (VEPs), while those whose scores were 29 or lower (ie, rated as poor or passable in most items) were classified as slightly empathetic physicians (SEPs).

Pain intensity was measured with a numerical rating scale (0-10) for the typical pain level within 7 days before each encounter. The long-term stability of CARE scores was assessed in patients who maintained the same physician for more than 24 months. The study showed the following results:

• The CARE score was inversely associated with pain intensity (P < .001).
• Pain intensity was lower in patients in the VEP group than those in the SEP group (6.3 vs 6.7; P < .001).
• The likelihood of having a more empathetic physician generally increased with the decrease in the cut point of the CARE score for greater or less empathy of the physician.
• The extent of the physician’s empathy effects exceeded that reported for nonpharmacological treatments, current opioid use, and lumbar spine surgery.
• The effects of the interaction of empathy with time tended to favor the VEP group with regard to pain but were not statistically significant.

Empathy is an essential aspect of the patient-physician relationship (particularly in delivering care), and these findings demonstrate its relevance in pain therapy. Empathy has high therapeutic value, compared with many pain treatments that are often recommended in clinical practice.

This story was translated from Univadis Italy, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Physicians who treat patients are potentially exposed to two opposing psychological processes: A positive feeling related to the experience of helping someone in need and, on the other hand, the adverse experience of seeing someone’s suffering and being frustrated about their inability to help. The ability to share the feelings of others is often referred to as empathy, while the ability to care for and show interest in others is the key aspect of compassion. Empathy makes it possible to share the positive and negative feelings of others in the same way: We can therefore feel happy when we indirectly share others’ joy and sad when we indirectly share others’ suffering.

Empathy in healthcare professionals is associated with patient satisfaction, diagnostic accuracy, adherence to treatment recommendations, clinical outcomes, clinical expertise, and physician retention. However, evidence indicates a tendency for empathy to decline during physicians’ training and specialization.
 

Estimating Empathy

Empathy studies are primarily based on observational data that include physician self-assessment or patient-perceived empathy. External evaluation of empathy by the recipient or observer is not the dominant approach, and a systematic review of the topic showed that, in 331 of the 470 studies examined (70.4%), individuals self-reported their level of empathy. The self-assessment system, particularly for doctors, is more likely to measure the doctor’s attitudes about empathy than empathy itself. The lack of correlation between physician and patient empathy assessments made it clear that patients cannot be disregarded when assessing physician empathy.

Consultation and Relational Empathy (CARE) is the primary assessment tool available to patients to measure physician empathy. It is a reliable and consistent system, particularly in primary care scenarios.

The CARE measure captures even small nuances of patient interactions with the physician and has been confirmed as a valuable tool in assessing the relational components of empathy.
 

Doctor-Patient Relationship

Communication with the physician is generally considered an important element of chronic pain care because it affects patient engagement and decision-making. A collaborative approach involving the patient and clinician in clinical decisions was associated with adherence to pain treatment and improved outcomes among patients with chronic lower back pain. The study conducted in a primary care setting of 1352 participants showed findings regarding physician empathy that did not necessarily involve a therapeutic alliance with the patient based on collaborative communication or expectation of a therapeutic effect of pharmacotherapy. Physician empathy remained the strongest factor associated with patient satisfaction, even after considering various potential confounders, including communication with the physician. In addition, ongoing empathy, especially when reported by patients with a long-term relationship with the physician, supported the hypothesis of a possible lasting effect on patient satisfaction.

Treating Chronic Pain

Empathy is an aspect of the doctor-patient relationship that may be particularly important in patients with chronic pain. A cohort study of 1470 patients with chronic low back pain analyzed whether and how it correlated with chronic pain outcomes. Patients reported their physician’s empathy at the time of enrollment using the CARE measure, which included 10 items on physician’s empathy characteristics during meetings. Physicians whose scores were 30 or higher (ie, rated as good, very good, or excellent in most items) were classified as very empathetic physicians (VEPs), while those whose scores were 29 or lower (ie, rated as poor or passable in most items) were classified as slightly empathetic physicians (SEPs).

Pain intensity was measured with a numerical rating scale (0-10) for the typical pain level within 7 days before each encounter. The long-term stability of CARE scores was assessed in patients who maintained the same physician for more than 24 months. The study showed the following results:

• The CARE score was inversely associated with pain intensity (P < .001).
• Pain intensity was lower in patients in the VEP group than those in the SEP group (6.3 vs 6.7; P < .001).
• The likelihood of having a more empathetic physician generally increased with the decrease in the cut point of the CARE score for greater or less empathy of the physician.
• The extent of the physician’s empathy effects exceeded that reported for nonpharmacological treatments, current opioid use, and lumbar spine surgery.
• The effects of the interaction of empathy with time tended to favor the VEP group with regard to pain but were not statistically significant.

Empathy is an essential aspect of the patient-physician relationship (particularly in delivering care), and these findings demonstrate its relevance in pain therapy. Empathy has high therapeutic value, compared with many pain treatments that are often recommended in clinical practice.

This story was translated from Univadis Italy, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Physicians who treat patients are potentially exposed to two opposing psychological processes: A positive feeling related to the experience of helping someone in need and, on the other hand, the adverse experience of seeing someone’s suffering and being frustrated about their inability to help. The ability to share the feelings of others is often referred to as empathy, while the ability to care for and show interest in others is the key aspect of compassion. Empathy makes it possible to share the positive and negative feelings of others in the same way: We can therefore feel happy when we indirectly share others’ joy and sad when we indirectly share others’ suffering.

Empathy in healthcare professionals is associated with patient satisfaction, diagnostic accuracy, adherence to treatment recommendations, clinical outcomes, clinical expertise, and physician retention. However, evidence indicates a tendency for empathy to decline during physicians’ training and specialization.
 

Estimating Empathy

Empathy studies are primarily based on observational data that include physician self-assessment or patient-perceived empathy. External evaluation of empathy by the recipient or observer is not the dominant approach, and a systematic review of the topic showed that, in 331 of the 470 studies examined (70.4%), individuals self-reported their level of empathy. The self-assessment system, particularly for doctors, is more likely to measure the doctor’s attitudes about empathy than empathy itself. The lack of correlation between physician and patient empathy assessments made it clear that patients cannot be disregarded when assessing physician empathy.

Consultation and Relational Empathy (CARE) is the primary assessment tool available to patients to measure physician empathy. It is a reliable and consistent system, particularly in primary care scenarios.

The CARE measure captures even small nuances of patient interactions with the physician and has been confirmed as a valuable tool in assessing the relational components of empathy.
 

Doctor-Patient Relationship

Communication with the physician is generally considered an important element of chronic pain care because it affects patient engagement and decision-making. A collaborative approach involving the patient and clinician in clinical decisions was associated with adherence to pain treatment and improved outcomes among patients with chronic lower back pain. The study conducted in a primary care setting of 1352 participants showed findings regarding physician empathy that did not necessarily involve a therapeutic alliance with the patient based on collaborative communication or expectation of a therapeutic effect of pharmacotherapy. Physician empathy remained the strongest factor associated with patient satisfaction, even after considering various potential confounders, including communication with the physician. In addition, ongoing empathy, especially when reported by patients with a long-term relationship with the physician, supported the hypothesis of a possible lasting effect on patient satisfaction.

Treating Chronic Pain

Empathy is an aspect of the doctor-patient relationship that may be particularly important in patients with chronic pain. A cohort study of 1470 patients with chronic low back pain analyzed whether and how it correlated with chronic pain outcomes. Patients reported their physician’s empathy at the time of enrollment using the CARE measure, which included 10 items on physician’s empathy characteristics during meetings. Physicians whose scores were 30 or higher (ie, rated as good, very good, or excellent in most items) were classified as very empathetic physicians (VEPs), while those whose scores were 29 or lower (ie, rated as poor or passable in most items) were classified as slightly empathetic physicians (SEPs).

Pain intensity was measured with a numerical rating scale (0-10) for the typical pain level within 7 days before each encounter. The long-term stability of CARE scores was assessed in patients who maintained the same physician for more than 24 months. The study showed the following results:

• The CARE score was inversely associated with pain intensity (P < .001).
• Pain intensity was lower in patients in the VEP group than those in the SEP group (6.3 vs 6.7; P < .001).
• The likelihood of having a more empathetic physician generally increased with the decrease in the cut point of the CARE score for greater or less empathy of the physician.
• The extent of the physician’s empathy effects exceeded that reported for nonpharmacological treatments, current opioid use, and lumbar spine surgery.
• The effects of the interaction of empathy with time tended to favor the VEP group with regard to pain but were not statistically significant.

Empathy is an essential aspect of the patient-physician relationship (particularly in delivering care), and these findings demonstrate its relevance in pain therapy. Empathy has high therapeutic value, compared with many pain treatments that are often recommended in clinical practice.

This story was translated from Univadis Italy, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Coffee and tea are among the plants that are highest in caffeine. Their use as beverages makes caffeine the most consumed psychoactive agent in the world. Coffee is commonly used to increase alertness and work productivity. Synthetic caffeine is added to soft drinks, energy drinks, and products intended to reduce fatigue or promote weight loss.

The caffeine content varies with the type of drink: It is high in coffee, energy drinks, and caffeine tablets; intermediate in tea; and low in soft drinks. Coffee is the predominant source of the caffeine ingested by adults. The evidence for caffeine’s effects on people is ambiguous, and some risks and benefits deserve special attention because of the impact they may have on our health.
 

Characteristics of Caffeine

Caffeine is a methylxanthine that is completely absorbed 45 minutes after ingestion, peaking between 15 minutes and 2 hours. The half-life of caffeine varies according to age. In adults, it is 2.5-4.5 hours; in newborns, 80 hours; in children older than 6 months, it remains stable over time with respect to weight. Smoking accelerates caffeine metabolism by reducing the half-life by 50%. Oral contraceptives, however, double caffeine’s half-life. Caffeine metabolism is reduced during pregnancy (it is greater in the first trimester), with a half-life of more than 15 hours. Caffeine clearance can be slowed by several classes of drugs (eg, quinolones, cardiovascular drugs, bronchodilators, and antidepressants) that increase its half-life because they are metabolized by the same liver enzymes.

Caffeine passes the blood-brain barrier and, having an adenosine-like structure, inhibits adenosine’s effects by binding to adenosine receptors. In the brain, caffeine reduces fatigue, increases alertness, reduces reaction times, may reduce the risk for depression, and increases the effectiveness of nonsteroidal anti-inflammatory drugs in treating headaches and other types of pain.
 

Caffeine and Chronic Diseases

The evidence available on the relationship between caffeine and health has several methodological limitations. Observations of the acute effects of caffeine may not reflect long-term effects because tolerance to caffeine’s effects may develop over time. Smoking and unhealthy lifestyles are confounding factors in epidemiological studies of caffeine intake. In addition, the estimate of the amount and frequency of caffeine intake is often inaccurate because it is mainly based on self-assessment systems. Finally, prospective studies of caffeine consumption are mainly based on coffee and tea consumption, but it is unclear how much the observed outcomes can be translated to intake of other beverages such as energy drinks.

Considering the very high prevalence of arterial hypertension worldwide (31.1% of adults), many questions have been raised about the influence of coffee consumption on blood pressure (BP) and the risk for arterial hypertension. Administration of 200-300 mg caffeine is shown to induce a mean increase of 8.1 mm Hg systolic BP and 5.7 mm Hg diastolic BP. The increase is observed in the first hour after caffeine intake and lasts no longer than 3 hours.

Yet, the moderate and usual consumption of coffee does not increase, but may even reduce, the risk of developing high BP. In contrast, occasional coffee consumption can have hypertensive effects, and moderate and usual consumption in patients with high BP does not appear to increase the risk for uncontrolled BP and can reduce the risk for death from any cause. The inverse association between coffee consumption and hypertension risk was confirmed in a review and meta-analysis of cross-sectional and cohort studies.

With respect to lipid metabolism, cholesterol levels may increase after caffeine consumption because of cafestol. Concentrations of cafestol are high in unfiltered coffee, intermediate in espresso and moka pot coffee, and negligible in instant or filtered coffee. Studies on the impact of coffee on lipid levels have led to inconsistent results, however. Data have shown that people who drink more coffee have higher triglycerides, total cholesterol, and low-density lipoprotein cholesterol (LDL-C) levels. Other data have shown that caffeine promotes LDL receptor expression and clearance of LDL cholesterol.

Experimental and cohort studies have not shown an association between coffee consumption and atrial fibrillation (AF). In fact, evidence suggests that coffee consumption tends to reduce the risk for AF in a dose-response relationship. Similarly, coffee consumption is not associated with increased risk for cardiovascular events in the general population or among patients with a history of hypertension, diabetes, or cardiovascular disease.

The Coffee and Real-Time Atrial and Ventricular Ectopy study evaluated the acute effects of coffee consumption on cardiac ectopy using wearable sensors with continuous recording. It did not demonstrate any increase in daily premature atrial contractions with coffee consumption, compared with abstaining from caffeine. 

In patients with type 2 diabetes, a study performed in Japan showed that coffee consumption was associated with reduced all-cause mortality. The results suggested a dose-response relationship, and drinking coffee and green tea appeared to reduce mortality risk further. The results were not generalizable, however, because of the study population’s ethnic homogeneity.
 

Dose and Toxicity

Caffeine at high doses (> 400 mg daily) and in susceptible patients can induce anxiety, but the effects of caffeine on sleep and anxiety can differ from patient to patient. This variation reflects differences in caffeine metabolism rate and adenosine receptor gene variants.

High caffeine intake can stimulate diuresis, but without causing damaging effects on hydration when taking moderate doses of caffeine (≤ 400 mg daily) for long periods. Stopping caffeine suddenly, in a regular consumer, can lead to withdrawal symptoms such as headache, asthenia, decreased attention, depressed mood, and flu-like symptoms.

The toxic effects of caffeine occur with intake > 1.2 g. A dose of 10-14 g is considered fatal. Caffeine overdose is rare when considering traditional methods of intake (coffee and tea) because 70-100 cups of coffee should be sufficient for caffeine poisoning. Severe events can occur following the use of caffeine tablets or as energy drinks for the following reasons:

• The episodic consumption of caffeine does not allow for tolerance to develop.
• Young people are more vulnerable to the effects of caffeine.
• Caffeine has a synergistic effect in combination with other components in energy drinks.
• Taking caffeine in combination with alcohol or intense exertion causes serious, even fatal, outcomes.

Products Containing Caffeine

Evidence supports the relationship between high consumption (approximately 1 L) of energy drinks with a caffeine content of 320 mg and short-term cardiovascular adverse events, such as increased BP, QT-segment prolongation corrected for heart rate, and palpitations. These tests prompt the recommendation to avoid consuming these beverages in high quantities and in association with alcohol.

Weight loss products generally contain caffeine coupled with herbal extracts that are expected to improve fat metabolism, lipolysis, and oxidation. These products, because of their easy availability, presumed benefits, and high caffeine concentration, may be more susceptible to misuse because they can be taken in larger portions than recommended. The combination of multiple ingredients, concentrated amounts of caffeine, and excessive consumption increases the likelihood of adverse effects.

This story was translated from Univadis Italy, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Coffee and tea are among the plants that are highest in caffeine. Their use as beverages makes caffeine the most consumed psychoactive agent in the world. Coffee is commonly used to increase alertness and work productivity. Synthetic caffeine is added to soft drinks, energy drinks, and products intended to reduce fatigue or promote weight loss.

The caffeine content varies with the type of drink: It is high in coffee, energy drinks, and caffeine tablets; intermediate in tea; and low in soft drinks. Coffee is the predominant source of the caffeine ingested by adults. The evidence for caffeine’s effects on people is ambiguous, and some risks and benefits deserve special attention because of the impact they may have on our health.
 

Characteristics of Caffeine

Caffeine is a methylxanthine that is completely absorbed 45 minutes after ingestion, peaking between 15 minutes and 2 hours. The half-life of caffeine varies according to age. In adults, it is 2.5-4.5 hours; in newborns, 80 hours; in children older than 6 months, it remains stable over time with respect to weight. Smoking accelerates caffeine metabolism by reducing the half-life by 50%. Oral contraceptives, however, double caffeine’s half-life. Caffeine metabolism is reduced during pregnancy (it is greater in the first trimester), with a half-life of more than 15 hours. Caffeine clearance can be slowed by several classes of drugs (eg, quinolones, cardiovascular drugs, bronchodilators, and antidepressants) that increase its half-life because they are metabolized by the same liver enzymes.

Caffeine passes the blood-brain barrier and, having an adenosine-like structure, inhibits adenosine’s effects by binding to adenosine receptors. In the brain, caffeine reduces fatigue, increases alertness, reduces reaction times, may reduce the risk for depression, and increases the effectiveness of nonsteroidal anti-inflammatory drugs in treating headaches and other types of pain.
 

Caffeine and Chronic Diseases

The evidence available on the relationship between caffeine and health has several methodological limitations. Observations of the acute effects of caffeine may not reflect long-term effects because tolerance to caffeine’s effects may develop over time. Smoking and unhealthy lifestyles are confounding factors in epidemiological studies of caffeine intake. In addition, the estimate of the amount and frequency of caffeine intake is often inaccurate because it is mainly based on self-assessment systems. Finally, prospective studies of caffeine consumption are mainly based on coffee and tea consumption, but it is unclear how much the observed outcomes can be translated to intake of other beverages such as energy drinks.

Considering the very high prevalence of arterial hypertension worldwide (31.1% of adults), many questions have been raised about the influence of coffee consumption on blood pressure (BP) and the risk for arterial hypertension. Administration of 200-300 mg caffeine is shown to induce a mean increase of 8.1 mm Hg systolic BP and 5.7 mm Hg diastolic BP. The increase is observed in the first hour after caffeine intake and lasts no longer than 3 hours.

Yet, the moderate and usual consumption of coffee does not increase, but may even reduce, the risk of developing high BP. In contrast, occasional coffee consumption can have hypertensive effects, and moderate and usual consumption in patients with high BP does not appear to increase the risk for uncontrolled BP and can reduce the risk for death from any cause. The inverse association between coffee consumption and hypertension risk was confirmed in a review and meta-analysis of cross-sectional and cohort studies.

With respect to lipid metabolism, cholesterol levels may increase after caffeine consumption because of cafestol. Concentrations of cafestol are high in unfiltered coffee, intermediate in espresso and moka pot coffee, and negligible in instant or filtered coffee. Studies on the impact of coffee on lipid levels have led to inconsistent results, however. Data have shown that people who drink more coffee have higher triglycerides, total cholesterol, and low-density lipoprotein cholesterol (LDL-C) levels. Other data have shown that caffeine promotes LDL receptor expression and clearance of LDL cholesterol.

Experimental and cohort studies have not shown an association between coffee consumption and atrial fibrillation (AF). In fact, evidence suggests that coffee consumption tends to reduce the risk for AF in a dose-response relationship. Similarly, coffee consumption is not associated with increased risk for cardiovascular events in the general population or among patients with a history of hypertension, diabetes, or cardiovascular disease.

The Coffee and Real-Time Atrial and Ventricular Ectopy study evaluated the acute effects of coffee consumption on cardiac ectopy using wearable sensors with continuous recording. It did not demonstrate any increase in daily premature atrial contractions with coffee consumption, compared with abstaining from caffeine. 

In patients with type 2 diabetes, a study performed in Japan showed that coffee consumption was associated with reduced all-cause mortality. The results suggested a dose-response relationship, and drinking coffee and green tea appeared to reduce mortality risk further. The results were not generalizable, however, because of the study population’s ethnic homogeneity.
 

Dose and Toxicity

Caffeine at high doses (> 400 mg daily) and in susceptible patients can induce anxiety, but the effects of caffeine on sleep and anxiety can differ from patient to patient. This variation reflects differences in caffeine metabolism rate and adenosine receptor gene variants.

High caffeine intake can stimulate diuresis, but without causing damaging effects on hydration when taking moderate doses of caffeine (≤ 400 mg daily) for long periods. Stopping caffeine suddenly, in a regular consumer, can lead to withdrawal symptoms such as headache, asthenia, decreased attention, depressed mood, and flu-like symptoms.

The toxic effects of caffeine occur with intake > 1.2 g. A dose of 10-14 g is considered fatal. Caffeine overdose is rare when considering traditional methods of intake (coffee and tea) because 70-100 cups of coffee should be sufficient for caffeine poisoning. Severe events can occur following the use of caffeine tablets or as energy drinks for the following reasons:

• The episodic consumption of caffeine does not allow for tolerance to develop.
• Young people are more vulnerable to the effects of caffeine.
• Caffeine has a synergistic effect in combination with other components in energy drinks.
• Taking caffeine in combination with alcohol or intense exertion causes serious, even fatal, outcomes.

Products Containing Caffeine

Evidence supports the relationship between high consumption (approximately 1 L) of energy drinks with a caffeine content of 320 mg and short-term cardiovascular adverse events, such as increased BP, QT-segment prolongation corrected for heart rate, and palpitations. These tests prompt the recommendation to avoid consuming these beverages in high quantities and in association with alcohol.

Weight loss products generally contain caffeine coupled with herbal extracts that are expected to improve fat metabolism, lipolysis, and oxidation. These products, because of their easy availability, presumed benefits, and high caffeine concentration, may be more susceptible to misuse because they can be taken in larger portions than recommended. The combination of multiple ingredients, concentrated amounts of caffeine, and excessive consumption increases the likelihood of adverse effects.

This story was translated from Univadis Italy, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Coffee and tea are among the plants that are highest in caffeine. Their use as beverages makes caffeine the most consumed psychoactive agent in the world. Coffee is commonly used to increase alertness and work productivity. Synthetic caffeine is added to soft drinks, energy drinks, and products intended to reduce fatigue or promote weight loss.

The caffeine content varies with the type of drink: It is high in coffee, energy drinks, and caffeine tablets; intermediate in tea; and low in soft drinks. Coffee is the predominant source of the caffeine ingested by adults. The evidence for caffeine’s effects on people is ambiguous, and some risks and benefits deserve special attention because of the impact they may have on our health.
 

Characteristics of Caffeine

Caffeine is a methylxanthine that is completely absorbed 45 minutes after ingestion, peaking between 15 minutes and 2 hours. The half-life of caffeine varies according to age. In adults, it is 2.5-4.5 hours; in newborns, 80 hours; in children older than 6 months, it remains stable over time with respect to weight. Smoking accelerates caffeine metabolism by reducing the half-life by 50%. Oral contraceptives, however, double caffeine’s half-life. Caffeine metabolism is reduced during pregnancy (it is greater in the first trimester), with a half-life of more than 15 hours. Caffeine clearance can be slowed by several classes of drugs (eg, quinolones, cardiovascular drugs, bronchodilators, and antidepressants) that increase its half-life because they are metabolized by the same liver enzymes.

Caffeine passes the blood-brain barrier and, having an adenosine-like structure, inhibits adenosine’s effects by binding to adenosine receptors. In the brain, caffeine reduces fatigue, increases alertness, reduces reaction times, may reduce the risk for depression, and increases the effectiveness of nonsteroidal anti-inflammatory drugs in treating headaches and other types of pain.
 

Caffeine and Chronic Diseases

The evidence available on the relationship between caffeine and health has several methodological limitations. Observations of the acute effects of caffeine may not reflect long-term effects because tolerance to caffeine’s effects may develop over time. Smoking and unhealthy lifestyles are confounding factors in epidemiological studies of caffeine intake. In addition, the estimate of the amount and frequency of caffeine intake is often inaccurate because it is mainly based on self-assessment systems. Finally, prospective studies of caffeine consumption are mainly based on coffee and tea consumption, but it is unclear how much the observed outcomes can be translated to intake of other beverages such as energy drinks.

Considering the very high prevalence of arterial hypertension worldwide (31.1% of adults), many questions have been raised about the influence of coffee consumption on blood pressure (BP) and the risk for arterial hypertension. Administration of 200-300 mg caffeine is shown to induce a mean increase of 8.1 mm Hg systolic BP and 5.7 mm Hg diastolic BP. The increase is observed in the first hour after caffeine intake and lasts no longer than 3 hours.

Yet, the moderate and usual consumption of coffee does not increase, but may even reduce, the risk of developing high BP. In contrast, occasional coffee consumption can have hypertensive effects, and moderate and usual consumption in patients with high BP does not appear to increase the risk for uncontrolled BP and can reduce the risk for death from any cause. The inverse association between coffee consumption and hypertension risk was confirmed in a review and meta-analysis of cross-sectional and cohort studies.

With respect to lipid metabolism, cholesterol levels may increase after caffeine consumption because of cafestol. Concentrations of cafestol are high in unfiltered coffee, intermediate in espresso and moka pot coffee, and negligible in instant or filtered coffee. Studies on the impact of coffee on lipid levels have led to inconsistent results, however. Data have shown that people who drink more coffee have higher triglycerides, total cholesterol, and low-density lipoprotein cholesterol (LDL-C) levels. Other data have shown that caffeine promotes LDL receptor expression and clearance of LDL cholesterol.

Experimental and cohort studies have not shown an association between coffee consumption and atrial fibrillation (AF). In fact, evidence suggests that coffee consumption tends to reduce the risk for AF in a dose-response relationship. Similarly, coffee consumption is not associated with increased risk for cardiovascular events in the general population or among patients with a history of hypertension, diabetes, or cardiovascular disease.

The Coffee and Real-Time Atrial and Ventricular Ectopy study evaluated the acute effects of coffee consumption on cardiac ectopy using wearable sensors with continuous recording. It did not demonstrate any increase in daily premature atrial contractions with coffee consumption, compared with abstaining from caffeine. 

In patients with type 2 diabetes, a study performed in Japan showed that coffee consumption was associated with reduced all-cause mortality. The results suggested a dose-response relationship, and drinking coffee and green tea appeared to reduce mortality risk further. The results were not generalizable, however, because of the study population’s ethnic homogeneity.
 

Dose and Toxicity

Caffeine at high doses (> 400 mg daily) and in susceptible patients can induce anxiety, but the effects of caffeine on sleep and anxiety can differ from patient to patient. This variation reflects differences in caffeine metabolism rate and adenosine receptor gene variants.

High caffeine intake can stimulate diuresis, but without causing damaging effects on hydration when taking moderate doses of caffeine (≤ 400 mg daily) for long periods. Stopping caffeine suddenly, in a regular consumer, can lead to withdrawal symptoms such as headache, asthenia, decreased attention, depressed mood, and flu-like symptoms.

The toxic effects of caffeine occur with intake > 1.2 g. A dose of 10-14 g is considered fatal. Caffeine overdose is rare when considering traditional methods of intake (coffee and tea) because 70-100 cups of coffee should be sufficient for caffeine poisoning. Severe events can occur following the use of caffeine tablets or as energy drinks for the following reasons:

• The episodic consumption of caffeine does not allow for tolerance to develop.
• Young people are more vulnerable to the effects of caffeine.
• Caffeine has a synergistic effect in combination with other components in energy drinks.
• Taking caffeine in combination with alcohol or intense exertion causes serious, even fatal, outcomes.

Products Containing Caffeine

Evidence supports the relationship between high consumption (approximately 1 L) of energy drinks with a caffeine content of 320 mg and short-term cardiovascular adverse events, such as increased BP, QT-segment prolongation corrected for heart rate, and palpitations. These tests prompt the recommendation to avoid consuming these beverages in high quantities and in association with alcohol.

Weight loss products generally contain caffeine coupled with herbal extracts that are expected to improve fat metabolism, lipolysis, and oxidation. These products, because of their easy availability, presumed benefits, and high caffeine concentration, may be more susceptible to misuse because they can be taken in larger portions than recommended. The combination of multiple ingredients, concentrated amounts of caffeine, and excessive consumption increases the likelihood of adverse effects.

This story was translated from Univadis Italy, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Crisugabalin — an oral calcium channel alpha 2 delta-1 subunit ligand — was safe and well-tolerated at doses of 40 mg/d and 80 mg/d and significantly reduced pain scores in patients with postherpetic neuralgia (PHN) over 12 weeks in a phase 3 study.

METHODOLOGY:

• Researchers conducted a phase 3 multicenter, double-blind study involving 366 patients in China (median age, 63 years; 52.7% men) with PHN with an average daily pain score (ADPS) of 4 or greater on the numeric pain rating scale who were randomly assigned to receive either crisugabalin 40 mg/d (n = 121), 80 mg/d (n = 121), or placebo (n = 124) for 12 weeks.
• Patients who did not experience any serious toxic effects in these 12 weeks entered a 14-week open-label extension phase and received crisugabalin 40 mg twice daily.
• The primary efficacy endpoint was the change in ADPS from baseline at week 12.
• Secondary efficacy endpoints included the proportion of patients achieving at least 30% and 50% reduction in ADPS at week 12; changes in the Short-Form McGill Pain Questionnaire (SF-MPQ), Visual Analog Scale, and Average Daily Sleep Interference Scale scores at week 12; and change in the SF-MPQ Present Pain Intensity scores at weeks 12 and 26.

TAKEAWAY:

• At week 12, among those on crisugabalin 40 mg/d and 80 mg/d, there were significant reductions in ADPS compared with placebo (least squares mean [LSM] change from baseline, −2.2 and −2.6 vs −1.1, respectively; P < .001).
• A greater proportion of patients on crisugabalin 40 mg/d (61.2%) and 80 mg/d (54.5%) achieved 30% or greater reduction in ADPS (P < .001) than patients who received placebo (35.5%). Similarly, a 50% or greater reduction in ADPS was achieved by 37.2% of patients on crisugabalin 40 mg/d (P = .002) and 38% on 80 mg/d (P < .001), compared with 20.2% for placebo.
• Crisugabalin 40 mg/d and crisugabalin 80 mg/d were associated with greater reductions in the pain intensity at week 12 than placebo (LSM, −1.0 and −1.2 vs −0.5, respectively; P < .001). Similar patterns were noted for other pain-related measures at weeks 12 and 26.
• Serious treatment-emergent adverse events occurred in four patients in each group; only 2.4% of those on 40 mg/d and 1.6% on 80 mg/d discontinued treatment because of side effects.

IN PRACTICE:

“Crisugabalin 40 mg/d or crisugabalin 80 mg/d was well-tolerated and significantly improved ADPS compared to placebo,” the authors wrote, adding that “crisugabalin can be flexibly selected depending on individual patient response and tolerability at 40 mg/d or 80 mg/d.”

SOURCE:

The study was led by Daying Zhang, PhD, of the Department of Pain Medicine at The First Affiliated Hospital of Nanchang University, Nanchang, China. It was published online in JAMA Dermatology.

LIMITATIONS:

The findings may not be generalizable to the global population as the study population was limited to Chinese patients. The study only provided short-term efficacy and safety data on crisugabalin, lacked an active comparator, and did not reflect the standard of care observed in the United States or Europe, where oral tricyclic antidepressants, pregabalin, and the lidocaine patch are recommended as first-line therapies.

DISCLOSURES:

The study was sponsored and funded by Haisco Pharmaceutical. Dr. Zhang and another author reported receiving support from Haisco. Two authors are company employees.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Crisugabalin — an oral calcium channel alpha 2 delta-1 subunit ligand — was safe and well-tolerated at doses of 40 mg/d and 80 mg/d and significantly reduced pain scores in patients with postherpetic neuralgia (PHN) over 12 weeks in a phase 3 study.

METHODOLOGY:

• Researchers conducted a phase 3 multicenter, double-blind study involving 366 patients in China (median age, 63 years; 52.7% men) with PHN with an average daily pain score (ADPS) of 4 or greater on the numeric pain rating scale who were randomly assigned to receive either crisugabalin 40 mg/d (n = 121), 80 mg/d (n = 121), or placebo (n = 124) for 12 weeks.
• Patients who did not experience any serious toxic effects in these 12 weeks entered a 14-week open-label extension phase and received crisugabalin 40 mg twice daily.
• The primary efficacy endpoint was the change in ADPS from baseline at week 12.
• Secondary efficacy endpoints included the proportion of patients achieving at least 30% and 50% reduction in ADPS at week 12; changes in the Short-Form McGill Pain Questionnaire (SF-MPQ), Visual Analog Scale, and Average Daily Sleep Interference Scale scores at week 12; and change in the SF-MPQ Present Pain Intensity scores at weeks 12 and 26.

TAKEAWAY:

• At week 12, among those on crisugabalin 40 mg/d and 80 mg/d, there were significant reductions in ADPS compared with placebo (least squares mean [LSM] change from baseline, −2.2 and −2.6 vs −1.1, respectively; P < .001).
• A greater proportion of patients on crisugabalin 40 mg/d (61.2%) and 80 mg/d (54.5%) achieved 30% or greater reduction in ADPS (P < .001) than patients who received placebo (35.5%). Similarly, a 50% or greater reduction in ADPS was achieved by 37.2% of patients on crisugabalin 40 mg/d (P = .002) and 38% on 80 mg/d (P < .001), compared with 20.2% for placebo.
• Crisugabalin 40 mg/d and crisugabalin 80 mg/d were associated with greater reductions in the pain intensity at week 12 than placebo (LSM, −1.0 and −1.2 vs −0.5, respectively; P < .001). Similar patterns were noted for other pain-related measures at weeks 12 and 26.
• Serious treatment-emergent adverse events occurred in four patients in each group; only 2.4% of those on 40 mg/d and 1.6% on 80 mg/d discontinued treatment because of side effects.

IN PRACTICE:

“Crisugabalin 40 mg/d or crisugabalin 80 mg/d was well-tolerated and significantly improved ADPS compared to placebo,” the authors wrote, adding that “crisugabalin can be flexibly selected depending on individual patient response and tolerability at 40 mg/d or 80 mg/d.”

SOURCE:

The study was led by Daying Zhang, PhD, of the Department of Pain Medicine at The First Affiliated Hospital of Nanchang University, Nanchang, China. It was published online in JAMA Dermatology.

LIMITATIONS:

The findings may not be generalizable to the global population as the study population was limited to Chinese patients. The study only provided short-term efficacy and safety data on crisugabalin, lacked an active comparator, and did not reflect the standard of care observed in the United States or Europe, where oral tricyclic antidepressants, pregabalin, and the lidocaine patch are recommended as first-line therapies.

DISCLOSURES:

The study was sponsored and funded by Haisco Pharmaceutical. Dr. Zhang and another author reported receiving support from Haisco. Two authors are company employees.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Crisugabalin — an oral calcium channel alpha 2 delta-1 subunit ligand — was safe and well-tolerated at doses of 40 mg/d and 80 mg/d and significantly reduced pain scores in patients with postherpetic neuralgia (PHN) over 12 weeks in a phase 3 study.

METHODOLOGY:

• Researchers conducted a phase 3 multicenter, double-blind study involving 366 patients in China (median age, 63 years; 52.7% men) with PHN with an average daily pain score (ADPS) of 4 or greater on the numeric pain rating scale who were randomly assigned to receive either crisugabalin 40 mg/d (n = 121), 80 mg/d (n = 121), or placebo (n = 124) for 12 weeks.
• Patients who did not experience any serious toxic effects in these 12 weeks entered a 14-week open-label extension phase and received crisugabalin 40 mg twice daily.
• The primary efficacy endpoint was the change in ADPS from baseline at week 12.
• Secondary efficacy endpoints included the proportion of patients achieving at least 30% and 50% reduction in ADPS at week 12; changes in the Short-Form McGill Pain Questionnaire (SF-MPQ), Visual Analog Scale, and Average Daily Sleep Interference Scale scores at week 12; and change in the SF-MPQ Present Pain Intensity scores at weeks 12 and 26.

TAKEAWAY:

• At week 12, among those on crisugabalin 40 mg/d and 80 mg/d, there were significant reductions in ADPS compared with placebo (least squares mean [LSM] change from baseline, −2.2 and −2.6 vs −1.1, respectively; P < .001).
• A greater proportion of patients on crisugabalin 40 mg/d (61.2%) and 80 mg/d (54.5%) achieved 30% or greater reduction in ADPS (P < .001) than patients who received placebo (35.5%). Similarly, a 50% or greater reduction in ADPS was achieved by 37.2% of patients on crisugabalin 40 mg/d (P = .002) and 38% on 80 mg/d (P < .001), compared with 20.2% for placebo.
• Crisugabalin 40 mg/d and crisugabalin 80 mg/d were associated with greater reductions in the pain intensity at week 12 than placebo (LSM, −1.0 and −1.2 vs −0.5, respectively; P < .001). Similar patterns were noted for other pain-related measures at weeks 12 and 26.
• Serious treatment-emergent adverse events occurred in four patients in each group; only 2.4% of those on 40 mg/d and 1.6% on 80 mg/d discontinued treatment because of side effects.

IN PRACTICE:

“Crisugabalin 40 mg/d or crisugabalin 80 mg/d was well-tolerated and significantly improved ADPS compared to placebo,” the authors wrote, adding that “crisugabalin can be flexibly selected depending on individual patient response and tolerability at 40 mg/d or 80 mg/d.”

SOURCE:

The study was led by Daying Zhang, PhD, of the Department of Pain Medicine at The First Affiliated Hospital of Nanchang University, Nanchang, China. It was published online in JAMA Dermatology.

LIMITATIONS:

The findings may not be generalizable to the global population as the study population was limited to Chinese patients. The study only provided short-term efficacy and safety data on crisugabalin, lacked an active comparator, and did not reflect the standard of care observed in the United States or Europe, where oral tricyclic antidepressants, pregabalin, and the lidocaine patch are recommended as first-line therapies.

DISCLOSURES:

The study was sponsored and funded by Haisco Pharmaceutical. Dr. Zhang and another author reported receiving support from Haisco. Two authors are company employees.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

In a recent study of 6 monthly injections of 140 mg erenumab (Aimovig, Amgen), most patients with chronic migraine and nonopioid medication overuse headache (MOH) achieved remission. Published online in JAMA Neurology, the study is the first prospective, double-blind, randomized, placebo-controlled attempt to investigate patients with chronic migraine and MOH related to nonopioid medications, according to lead author Stewart J. Tepper, MD, and his coauthors.

Prior Studies Did Not Focus on MOH

Several prior phase 2 and 3 trials of calcitonin gene-related peptide (CGRP) ligand or receptor inhibitors that have been FDA-approved for migraine prevention have been performed. These drugs include erenumab, fremanezumab (Ajovy, Teva), galcanezumab (Emgality, Lilly), and eptinezumab (Vyepti, Lundbeck), for patients with and without medication overuse, said Alan M. Rapoport, MD, who was not involved with the new study. Dr. Rapoport is a clinical professor of neurology at the David Geffen School of Medicine of the University of California, in Los Angeles; past president of the International Headache Society; and founder and director emeritus of The New England Center for Headache in Stamford, Connecticut.

“But we could not call them patients with MOH because they weren’t studied prospectively, so that they had medication overuse according to International Classification of Headache Disorders (ICHD-3) criteria,” said Dr. Rapoport.

Phase 4, Randomized, Placebo-Controlled Trial

In the present clinical trial, investigators enrolled 584 patients with nonopioid MOH and history of failing at least one preventive treatment. After a 4-week baseline phase, researchers randomized patients 1:1:1 to 6 months’ treatment with erenumab 70 mg, erenumab 140 mg, or placebo.

Investigators defined remission as either of the following through months 4-6:

• < 10 mean monthly acute headache medication days per month (AHMD)
• < 14 mean monthly headache days (MHD)

In the primary analysis, 69.1% of patients in the 140 mg cohort achieved remission (P < .001) versus placebo. Remission rates in the 70 mg and the placebo cohorts were 60.3% (P < .13) and 52.6%, respectively. AHMD for the 140-mg, 70-mg, and placebo groups fell by 9.4, 7.8, and 6.6 days per month, respectively. Migraine Physical Function Impact Diary (non-EU sites) and Headache Impact Test-6 (EU sites) scores also showed greater improvement for patients treated with erenumab.

No new safety signals emerged, although erenumab-treated participants experienced 2-2.5 times as much COVID-19 disease.

Regarding the primary endpoint, said Dr. Rapoport, the 70-mg dose might also have yielded statistically significant improvement over placebo with a larger sample size. “I have seen that the higher dose of erenumab can be superior for efficacy than the lower in some of the double-blind trials,” he said. The 52.6% placebo response rate was rather high, he added, but not necessarily higher than in other migraine prevention trials.

“Placebo is a type of treatment,” Dr. Rapoport said. “It’s not as strong as the actual medication, which is specific for prevention, but it does work on the brain to some extent.”

He was more concerned, however, that authors did not counsel study patients about reducing or discontinuing their overused medications in a unified manner. Rather, it was left to individual investigators’ discretion, in different countries, as to whether to educate patients about the harms of medication overuse. “The fascinating aspect of this paper was that no patient was asked to detoxify from the overused medication,” said Dr. Rapoport, “and yet so many patients no longer had MOH at 6 months.”
 

Detox Versus No Detox

In a pioneering study of migraine medication overuse headache (then called rebound headache) published by Lee Kudrow, MD, in Advances in Neurology in 1982, patients who discontinued the overused medication fared much better than those who did not. Adding amitriptyline for migraine prevention further improved results, mostly in those who discontinued their overused medication.

Anticipating possible concerns, the authors wrote that their approach “may also be seen as a strength, as it represents a scenario closer to real life and avoids undue interference with the physician-patient relationship.” Indeed, said Dr. Rapoport, study results are perhaps more impressive because they were achieved through treatment with erenumab alone, without detoxification.
 

Managing Chronic Migraine and MOH

Until erenumab’s 2018 approval, migraine prevention options were limited to tricyclic antidepressants, beta blockers, and antiseizure medicines – though these medicines never seemed to work very well without detoxification, said Dr. Rapoport. Neurologists still use these categories for migraine prevention, he added, “because insurance companies insist that before we give the more expensive, newer medications like those that block CGRP, patients must fail 2 of those 3 categories of older medications which are not approved for chronic migraine.” Only onabotulinumtoxinA (Botox) is FDA-approved for chronic migraine. “There has been no head-to-head comparison of it and any of the monoclonal antibodies against CGRP,” he said.

In a March 2024 publication in Headache, the American Headache Society stated that requiring patients to fail older drugs is inappropriate, and that CGRP inhibitors, though costly, should be first-line for headache prevention. The key advantage of any drug that blocks CGRP in treating MOH is that unlike older drugs, CGRP inhibitors appear to work well even without detoxification, said Dr. Rapoport.

Additional study limitations included the possibility that the 24-week treatment period might not have allowed complete evaluation of long-term efficacy, the authors wrote. “These are usually pretty sick patients,” said Dr. Rapoport, who acknowledged the difficulty of keeping placebo patients off preventive medication altogether for 6 months. The study was extended to 12 months, and the results of an opiate overusers cohort also will be published.

Authors noted that according to a study published in Headache in 2022, most Americans with chronic migraine commonly go without preventive medications. Moreover, such medications do not always work. Accordingly, Dr. Rapoport said, the study duration was reasonable provided patients understood that they had a 33% chance of receiving no effective preventive medication over 6 months.

Extending the study’s month-long baseline period to 3 months before starting erenumab might have been helpful, he added, as that is the timeframe required to confirm MOH diagnosis according to ICHD-3. “However,” said Dr. Rapoport, “3 months with only usual medications, and then 1/3 of patients going 6-12 months with only placebo, would be tough for some patients.”

Dr. Rapoport reports no relevant financial conflicts.

In a recent study of 6 monthly injections of 140 mg erenumab (Aimovig, Amgen), most patients with chronic migraine and nonopioid medication overuse headache (MOH) achieved remission. Published online in JAMA Neurology, the study is the first prospective, double-blind, randomized, placebo-controlled attempt to investigate patients with chronic migraine and MOH related to nonopioid medications, according to lead author Stewart J. Tepper, MD, and his coauthors.

Prior Studies Did Not Focus on MOH

Several prior phase 2 and 3 trials of calcitonin gene-related peptide (CGRP) ligand or receptor inhibitors that have been FDA-approved for migraine prevention have been performed. These drugs include erenumab, fremanezumab (Ajovy, Teva), galcanezumab (Emgality, Lilly), and eptinezumab (Vyepti, Lundbeck), for patients with and without medication overuse, said Alan M. Rapoport, MD, who was not involved with the new study. Dr. Rapoport is a clinical professor of neurology at the David Geffen School of Medicine of the University of California, in Los Angeles; past president of the International Headache Society; and founder and director emeritus of The New England Center for Headache in Stamford, Connecticut.

“But we could not call them patients with MOH because they weren’t studied prospectively, so that they had medication overuse according to International Classification of Headache Disorders (ICHD-3) criteria,” said Dr. Rapoport.

Phase 4, Randomized, Placebo-Controlled Trial

In the present clinical trial, investigators enrolled 584 patients with nonopioid MOH and history of failing at least one preventive treatment. After a 4-week baseline phase, researchers randomized patients 1:1:1 to 6 months’ treatment with erenumab 70 mg, erenumab 140 mg, or placebo.

Investigators defined remission as either of the following through months 4-6:

• < 10 mean monthly acute headache medication days per month (AHMD)
• < 14 mean monthly headache days (MHD)

In the primary analysis, 69.1% of patients in the 140 mg cohort achieved remission (P < .001) versus placebo. Remission rates in the 70 mg and the placebo cohorts were 60.3% (P < .13) and 52.6%, respectively. AHMD for the 140-mg, 70-mg, and placebo groups fell by 9.4, 7.8, and 6.6 days per month, respectively. Migraine Physical Function Impact Diary (non-EU sites) and Headache Impact Test-6 (EU sites) scores also showed greater improvement for patients treated with erenumab.

No new safety signals emerged, although erenumab-treated participants experienced 2-2.5 times as much COVID-19 disease.

Regarding the primary endpoint, said Dr. Rapoport, the 70-mg dose might also have yielded statistically significant improvement over placebo with a larger sample size. “I have seen that the higher dose of erenumab can be superior for efficacy than the lower in some of the double-blind trials,” he said. The 52.6% placebo response rate was rather high, he added, but not necessarily higher than in other migraine prevention trials.

“Placebo is a type of treatment,” Dr. Rapoport said. “It’s not as strong as the actual medication, which is specific for prevention, but it does work on the brain to some extent.”

He was more concerned, however, that authors did not counsel study patients about reducing or discontinuing their overused medications in a unified manner. Rather, it was left to individual investigators’ discretion, in different countries, as to whether to educate patients about the harms of medication overuse. “The fascinating aspect of this paper was that no patient was asked to detoxify from the overused medication,” said Dr. Rapoport, “and yet so many patients no longer had MOH at 6 months.”
 

Detox Versus No Detox

In a pioneering study of migraine medication overuse headache (then called rebound headache) published by Lee Kudrow, MD, in Advances in Neurology in 1982, patients who discontinued the overused medication fared much better than those who did not. Adding amitriptyline for migraine prevention further improved results, mostly in those who discontinued their overused medication.

Anticipating possible concerns, the authors wrote that their approach “may also be seen as a strength, as it represents a scenario closer to real life and avoids undue interference with the physician-patient relationship.” Indeed, said Dr. Rapoport, study results are perhaps more impressive because they were achieved through treatment with erenumab alone, without detoxification.
 

Managing Chronic Migraine and MOH

Until erenumab’s 2018 approval, migraine prevention options were limited to tricyclic antidepressants, beta blockers, and antiseizure medicines – though these medicines never seemed to work very well without detoxification, said Dr. Rapoport. Neurologists still use these categories for migraine prevention, he added, “because insurance companies insist that before we give the more expensive, newer medications like those that block CGRP, patients must fail 2 of those 3 categories of older medications which are not approved for chronic migraine.” Only onabotulinumtoxinA (Botox) is FDA-approved for chronic migraine. “There has been no head-to-head comparison of it and any of the monoclonal antibodies against CGRP,” he said.

In a March 2024 publication in Headache, the American Headache Society stated that requiring patients to fail older drugs is inappropriate, and that CGRP inhibitors, though costly, should be first-line for headache prevention. The key advantage of any drug that blocks CGRP in treating MOH is that unlike older drugs, CGRP inhibitors appear to work well even without detoxification, said Dr. Rapoport.

Additional study limitations included the possibility that the 24-week treatment period might not have allowed complete evaluation of long-term efficacy, the authors wrote. “These are usually pretty sick patients,” said Dr. Rapoport, who acknowledged the difficulty of keeping placebo patients off preventive medication altogether for 6 months. The study was extended to 12 months, and the results of an opiate overusers cohort also will be published.

Authors noted that according to a study published in Headache in 2022, most Americans with chronic migraine commonly go without preventive medications. Moreover, such medications do not always work. Accordingly, Dr. Rapoport said, the study duration was reasonable provided patients understood that they had a 33% chance of receiving no effective preventive medication over 6 months.

Extending the study’s month-long baseline period to 3 months before starting erenumab might have been helpful, he added, as that is the timeframe required to confirm MOH diagnosis according to ICHD-3. “However,” said Dr. Rapoport, “3 months with only usual medications, and then 1/3 of patients going 6-12 months with only placebo, would be tough for some patients.”

Dr. Rapoport reports no relevant financial conflicts.

In a recent study of 6 monthly injections of 140 mg erenumab (Aimovig, Amgen), most patients with chronic migraine and nonopioid medication overuse headache (MOH) achieved remission. Published online in JAMA Neurology, the study is the first prospective, double-blind, randomized, placebo-controlled attempt to investigate patients with chronic migraine and MOH related to nonopioid medications, according to lead author Stewart J. Tepper, MD, and his coauthors.

Prior Studies Did Not Focus on MOH

Several prior phase 2 and 3 trials of calcitonin gene-related peptide (CGRP) ligand or receptor inhibitors that have been FDA-approved for migraine prevention have been performed. These drugs include erenumab, fremanezumab (Ajovy, Teva), galcanezumab (Emgality, Lilly), and eptinezumab (Vyepti, Lundbeck), for patients with and without medication overuse, said Alan M. Rapoport, MD, who was not involved with the new study. Dr. Rapoport is a clinical professor of neurology at the David Geffen School of Medicine of the University of California, in Los Angeles; past president of the International Headache Society; and founder and director emeritus of The New England Center for Headache in Stamford, Connecticut.

“But we could not call them patients with MOH because they weren’t studied prospectively, so that they had medication overuse according to International Classification of Headache Disorders (ICHD-3) criteria,” said Dr. Rapoport.

Phase 4, Randomized, Placebo-Controlled Trial

In the present clinical trial, investigators enrolled 584 patients with nonopioid MOH and history of failing at least one preventive treatment. After a 4-week baseline phase, researchers randomized patients 1:1:1 to 6 months’ treatment with erenumab 70 mg, erenumab 140 mg, or placebo.

Investigators defined remission as either of the following through months 4-6:

• < 10 mean monthly acute headache medication days per month (AHMD)
• < 14 mean monthly headache days (MHD)

In the primary analysis, 69.1% of patients in the 140 mg cohort achieved remission (P < .001) versus placebo. Remission rates in the 70 mg and the placebo cohorts were 60.3% (P < .13) and 52.6%, respectively. AHMD for the 140-mg, 70-mg, and placebo groups fell by 9.4, 7.8, and 6.6 days per month, respectively. Migraine Physical Function Impact Diary (non-EU sites) and Headache Impact Test-6 (EU sites) scores also showed greater improvement for patients treated with erenumab.

No new safety signals emerged, although erenumab-treated participants experienced 2-2.5 times as much COVID-19 disease.

Regarding the primary endpoint, said Dr. Rapoport, the 70-mg dose might also have yielded statistically significant improvement over placebo with a larger sample size. “I have seen that the higher dose of erenumab can be superior for efficacy than the lower in some of the double-blind trials,” he said. The 52.6% placebo response rate was rather high, he added, but not necessarily higher than in other migraine prevention trials.

“Placebo is a type of treatment,” Dr. Rapoport said. “It’s not as strong as the actual medication, which is specific for prevention, but it does work on the brain to some extent.”

He was more concerned, however, that authors did not counsel study patients about reducing or discontinuing their overused medications in a unified manner. Rather, it was left to individual investigators’ discretion, in different countries, as to whether to educate patients about the harms of medication overuse. “The fascinating aspect of this paper was that no patient was asked to detoxify from the overused medication,” said Dr. Rapoport, “and yet so many patients no longer had MOH at 6 months.”
 

Detox Versus No Detox

In a pioneering study of migraine medication overuse headache (then called rebound headache) published by Lee Kudrow, MD, in Advances in Neurology in 1982, patients who discontinued the overused medication fared much better than those who did not. Adding amitriptyline for migraine prevention further improved results, mostly in those who discontinued their overused medication.

Anticipating possible concerns, the authors wrote that their approach “may also be seen as a strength, as it represents a scenario closer to real life and avoids undue interference with the physician-patient relationship.” Indeed, said Dr. Rapoport, study results are perhaps more impressive because they were achieved through treatment with erenumab alone, without detoxification.
 

Managing Chronic Migraine and MOH

Until erenumab’s 2018 approval, migraine prevention options were limited to tricyclic antidepressants, beta blockers, and antiseizure medicines – though these medicines never seemed to work very well without detoxification, said Dr. Rapoport. Neurologists still use these categories for migraine prevention, he added, “because insurance companies insist that before we give the more expensive, newer medications like those that block CGRP, patients must fail 2 of those 3 categories of older medications which are not approved for chronic migraine.” Only onabotulinumtoxinA (Botox) is FDA-approved for chronic migraine. “There has been no head-to-head comparison of it and any of the monoclonal antibodies against CGRP,” he said.

In a March 2024 publication in Headache, the American Headache Society stated that requiring patients to fail older drugs is inappropriate, and that CGRP inhibitors, though costly, should be first-line for headache prevention. The key advantage of any drug that blocks CGRP in treating MOH is that unlike older drugs, CGRP inhibitors appear to work well even without detoxification, said Dr. Rapoport.

Additional study limitations included the possibility that the 24-week treatment period might not have allowed complete evaluation of long-term efficacy, the authors wrote. “These are usually pretty sick patients,” said Dr. Rapoport, who acknowledged the difficulty of keeping placebo patients off preventive medication altogether for 6 months. The study was extended to 12 months, and the results of an opiate overusers cohort also will be published.

Authors noted that according to a study published in Headache in 2022, most Americans with chronic migraine commonly go without preventive medications. Moreover, such medications do not always work. Accordingly, Dr. Rapoport said, the study duration was reasonable provided patients understood that they had a 33% chance of receiving no effective preventive medication over 6 months.

Extending the study’s month-long baseline period to 3 months before starting erenumab might have been helpful, he added, as that is the timeframe required to confirm MOH diagnosis according to ICHD-3. “However,” said Dr. Rapoport, “3 months with only usual medications, and then 1/3 of patients going 6-12 months with only placebo, would be tough for some patients.”

Dr. Rapoport reports no relevant financial conflicts.

TOPLINE:

The long-term use of muscle relaxants may benefit patients with painful spasms or cramps and neck pain, according to a systematic review of clinical studies, but they do not appear to be beneficial for low back pain, fibromyalgia, or headaches and can have adverse effects such as sedation and dry mouth.

METHODOLOGY:

• Researchers conducted a systematic review to evaluate the effectiveness of long-term use (≥ 4 weeks) of muscle relaxants for chronic pain lasting ≥ 3 months.
• They identified 30 randomized clinical trials involving 1314 patients and 14 cohort studies involving 1168 patients, grouped according to the categories of low back pain, fibromyalgia, painful cramps or spasticity, headaches, and other syndromes.
• Baclofen, tizanidine, cyclobenzaprine, eperisone, quinine, carisoprodol, orphenadrine, chlormezanone, and methocarbamol were the muscle relaxants assessed in comparison with placebo, other treatments, or untreated individuals.

TAKEAWAY:

• The long-term use of muscle relaxants reduced pain intensity in those with painful spasms or cramps and neck pain. Baclofen, orphenadrine, carisoprodol, and methocarbamol improved cramp frequency, while the use of eperisone and chlormezanone improved neck pain and enhanced the quality of sleep, respectively, in those with neck osteoarthritis.
• While some studies suggested that muscle relaxants reduced pain intensity in those with back pain and fibromyalgia, between-group differences were not observed. The benefits seen with some medications diminished after their discontinuation.
• Despite tizanidine improving pain severity in headaches, 25% participants dropped out owing to adverse effects. Although certain muscle relaxants demonstrated pain relief, others did not.
• The most common adverse effects of muscle relaxants were somnolence and dry mouth. Other adverse events included vomiting, diarrhea, nausea, weakness, and constipation.

IN PRACTICE:

“For patients already prescribed long-term SMRs [skeletal muscle relaxants], interventions are needed to assist clinicians to engage in shared decision-making with patients about deprescribing SMRs. This may be particularly true for older patients for whom risks of adverse events may be greater,” the authors wrote. “Clinicians should be vigilant for adverse effects and consider deprescribing if pain-related goals are not met.”

SOURCE:

The study, led by Benjamin J. Oldfield, MD, MHS, Yale School of Medicine, New Haven, Connecticut, was published online on September 19, 2024, in JAMA Network Open

LIMITATIONS:

This systematic review was limited to publications written in English, Spanish, and Italian language, potentially excluding studies from other regions. Variations in clinical sites, definitions of pain syndromes, medications, and durations of therapy prevented the possibility of conducting meta-analyses. Only quantitative studies were included, excluding valuable insights into patient experiences offered by qualitative studies. 

DISCLOSURES:

The study was supported by the National Institute on Drug Abuse. The authors declared no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

The long-term use of muscle relaxants may benefit patients with painful spasms or cramps and neck pain, according to a systematic review of clinical studies, but they do not appear to be beneficial for low back pain, fibromyalgia, or headaches and can have adverse effects such as sedation and dry mouth.

METHODOLOGY:

• Researchers conducted a systematic review to evaluate the effectiveness of long-term use (≥ 4 weeks) of muscle relaxants for chronic pain lasting ≥ 3 months.
• They identified 30 randomized clinical trials involving 1314 patients and 14 cohort studies involving 1168 patients, grouped according to the categories of low back pain, fibromyalgia, painful cramps or spasticity, headaches, and other syndromes.
• Baclofen, tizanidine, cyclobenzaprine, eperisone, quinine, carisoprodol, orphenadrine, chlormezanone, and methocarbamol were the muscle relaxants assessed in comparison with placebo, other treatments, or untreated individuals.

TAKEAWAY:

• The long-term use of muscle relaxants reduced pain intensity in those with painful spasms or cramps and neck pain. Baclofen, orphenadrine, carisoprodol, and methocarbamol improved cramp frequency, while the use of eperisone and chlormezanone improved neck pain and enhanced the quality of sleep, respectively, in those with neck osteoarthritis.
• While some studies suggested that muscle relaxants reduced pain intensity in those with back pain and fibromyalgia, between-group differences were not observed. The benefits seen with some medications diminished after their discontinuation.
• Despite tizanidine improving pain severity in headaches, 25% participants dropped out owing to adverse effects. Although certain muscle relaxants demonstrated pain relief, others did not.
• The most common adverse effects of muscle relaxants were somnolence and dry mouth. Other adverse events included vomiting, diarrhea, nausea, weakness, and constipation.

IN PRACTICE:

“For patients already prescribed long-term SMRs [skeletal muscle relaxants], interventions are needed to assist clinicians to engage in shared decision-making with patients about deprescribing SMRs. This may be particularly true for older patients for whom risks of adverse events may be greater,” the authors wrote. “Clinicians should be vigilant for adverse effects and consider deprescribing if pain-related goals are not met.”

SOURCE:

The study, led by Benjamin J. Oldfield, MD, MHS, Yale School of Medicine, New Haven, Connecticut, was published online on September 19, 2024, in JAMA Network Open

LIMITATIONS:

This systematic review was limited to publications written in English, Spanish, and Italian language, potentially excluding studies from other regions. Variations in clinical sites, definitions of pain syndromes, medications, and durations of therapy prevented the possibility of conducting meta-analyses. Only quantitative studies were included, excluding valuable insights into patient experiences offered by qualitative studies. 

DISCLOSURES:

The study was supported by the National Institute on Drug Abuse. The authors declared no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

The long-term use of muscle relaxants may benefit patients with painful spasms or cramps and neck pain, according to a systematic review of clinical studies, but they do not appear to be beneficial for low back pain, fibromyalgia, or headaches and can have adverse effects such as sedation and dry mouth.

METHODOLOGY:

• Researchers conducted a systematic review to evaluate the effectiveness of long-term use (≥ 4 weeks) of muscle relaxants for chronic pain lasting ≥ 3 months.
• They identified 30 randomized clinical trials involving 1314 patients and 14 cohort studies involving 1168 patients, grouped according to the categories of low back pain, fibromyalgia, painful cramps or spasticity, headaches, and other syndromes.
• Baclofen, tizanidine, cyclobenzaprine, eperisone, quinine, carisoprodol, orphenadrine, chlormezanone, and methocarbamol were the muscle relaxants assessed in comparison with placebo, other treatments, or untreated individuals.

TAKEAWAY:

• The long-term use of muscle relaxants reduced pain intensity in those with painful spasms or cramps and neck pain. Baclofen, orphenadrine, carisoprodol, and methocarbamol improved cramp frequency, while the use of eperisone and chlormezanone improved neck pain and enhanced the quality of sleep, respectively, in those with neck osteoarthritis.
• While some studies suggested that muscle relaxants reduced pain intensity in those with back pain and fibromyalgia, between-group differences were not observed. The benefits seen with some medications diminished after their discontinuation.
• Despite tizanidine improving pain severity in headaches, 25% participants dropped out owing to adverse effects. Although certain muscle relaxants demonstrated pain relief, others did not.
• The most common adverse effects of muscle relaxants were somnolence and dry mouth. Other adverse events included vomiting, diarrhea, nausea, weakness, and constipation.

IN PRACTICE:

“For patients already prescribed long-term SMRs [skeletal muscle relaxants], interventions are needed to assist clinicians to engage in shared decision-making with patients about deprescribing SMRs. This may be particularly true for older patients for whom risks of adverse events may be greater,” the authors wrote. “Clinicians should be vigilant for adverse effects and consider deprescribing if pain-related goals are not met.”

SOURCE:

The study, led by Benjamin J. Oldfield, MD, MHS, Yale School of Medicine, New Haven, Connecticut, was published online on September 19, 2024, in JAMA Network Open

LIMITATIONS:

This systematic review was limited to publications written in English, Spanish, and Italian language, potentially excluding studies from other regions. Variations in clinical sites, definitions of pain syndromes, medications, and durations of therapy prevented the possibility of conducting meta-analyses. Only quantitative studies were included, excluding valuable insights into patient experiences offered by qualitative studies. 

DISCLOSURES:

The study was supported by the National Institute on Drug Abuse. The authors declared no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Hypnosis reduces pain during sharp debridement of skin ulcers in patients with immune-mediated inflammatory diseases, with most patients reporting decreased pain awareness and lasting pain relief for 2-3 days after the procedure.

METHODOLOGY:

• Researchers reported their experience with the anecdotal use of hypnosis for pain management in debridement of skin ulcers in immune-mediated inflammatory diseases.
• They studied 16 participants (14 women; mean age, 56 years; 14 with systemic sclerosis or morphea) with recurrent skin ulcerations requiring sharp debridement, who presented to a wound care clinic at the Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom. The participants had negative experiences with pharmacologic pain management.
• Participants consented to hypnosis during debridement as the only mode of analgesia, conducted by the same hypnosis-trained, experienced healthcare professional in charge of their ulcer care.
• Ulcer pain scores were recorded using a numerical rating pain scale before and immediately after debridement, with a score of 0 indicating no pain and 10 indicating worst pain.

TAKEAWAY:

• Hypnosis reduced the median pre-debridement ulcer pain score from 8 (interquartile range [IQR], 7-10) to 0.5 (IQR, 0-2) immediately after the procedure.
• Of 16 participants, 14 reported being aware of the procedure but not feeling the pain, with only two participants experiencing a brief spike in pain.
• The other two participants reported experiencing reduced awareness and being pain-free during the procedure.
• Five participants reported a lasting decrease in pain perception for 2-3 days after the procedure.

IN PRACTICE:

“These preliminary data underscore the potential for the integration of hypnosis into the management of intervention-related pain in clinical care,” the authors wrote.

SOURCE:

The study was led by Begonya Alcacer-Pitarch, PhD, Leeds Institute of Rheumatic and Musculoskeletal Medicine, the University of Leeds, and Chapel Allerton Hospital in Leeds, United Kingdom. It was published as a correspondence on September 10, 2024, in The Lancet Rheumatology.

LIMITATIONS:

The small sample size may limit the generalizability of the findings. The methods used for data collection were not standardized, and the individuals included in the study may have introduced selection bias.

DISCLOSURES:

The study did not have a funding source. The authors declared no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Hypnosis reduces pain during sharp debridement of skin ulcers in patients with immune-mediated inflammatory diseases, with most patients reporting decreased pain awareness and lasting pain relief for 2-3 days after the procedure.

METHODOLOGY:

• Researchers reported their experience with the anecdotal use of hypnosis for pain management in debridement of skin ulcers in immune-mediated inflammatory diseases.
• They studied 16 participants (14 women; mean age, 56 years; 14 with systemic sclerosis or morphea) with recurrent skin ulcerations requiring sharp debridement, who presented to a wound care clinic at the Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom. The participants had negative experiences with pharmacologic pain management.
• Participants consented to hypnosis during debridement as the only mode of analgesia, conducted by the same hypnosis-trained, experienced healthcare professional in charge of their ulcer care.
• Ulcer pain scores were recorded using a numerical rating pain scale before and immediately after debridement, with a score of 0 indicating no pain and 10 indicating worst pain.

TAKEAWAY:

• Hypnosis reduced the median pre-debridement ulcer pain score from 8 (interquartile range [IQR], 7-10) to 0.5 (IQR, 0-2) immediately after the procedure.
• Of 16 participants, 14 reported being aware of the procedure but not feeling the pain, with only two participants experiencing a brief spike in pain.
• The other two participants reported experiencing reduced awareness and being pain-free during the procedure.
• Five participants reported a lasting decrease in pain perception for 2-3 days after the procedure.

IN PRACTICE:

“These preliminary data underscore the potential for the integration of hypnosis into the management of intervention-related pain in clinical care,” the authors wrote.

SOURCE:

The study was led by Begonya Alcacer-Pitarch, PhD, Leeds Institute of Rheumatic and Musculoskeletal Medicine, the University of Leeds, and Chapel Allerton Hospital in Leeds, United Kingdom. It was published as a correspondence on September 10, 2024, in The Lancet Rheumatology.

LIMITATIONS:

The small sample size may limit the generalizability of the findings. The methods used for data collection were not standardized, and the individuals included in the study may have introduced selection bias.

DISCLOSURES:

The study did not have a funding source. The authors declared no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Hypnosis reduces pain during sharp debridement of skin ulcers in patients with immune-mediated inflammatory diseases, with most patients reporting decreased pain awareness and lasting pain relief for 2-3 days after the procedure.

METHODOLOGY:

• Researchers reported their experience with the anecdotal use of hypnosis for pain management in debridement of skin ulcers in immune-mediated inflammatory diseases.
• They studied 16 participants (14 women; mean age, 56 years; 14 with systemic sclerosis or morphea) with recurrent skin ulcerations requiring sharp debridement, who presented to a wound care clinic at the Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom. The participants had negative experiences with pharmacologic pain management.
• Participants consented to hypnosis during debridement as the only mode of analgesia, conducted by the same hypnosis-trained, experienced healthcare professional in charge of their ulcer care.
• Ulcer pain scores were recorded using a numerical rating pain scale before and immediately after debridement, with a score of 0 indicating no pain and 10 indicating worst pain.

TAKEAWAY:

• Hypnosis reduced the median pre-debridement ulcer pain score from 8 (interquartile range [IQR], 7-10) to 0.5 (IQR, 0-2) immediately after the procedure.
• Of 16 participants, 14 reported being aware of the procedure but not feeling the pain, with only two participants experiencing a brief spike in pain.
• The other two participants reported experiencing reduced awareness and being pain-free during the procedure.
• Five participants reported a lasting decrease in pain perception for 2-3 days after the procedure.

IN PRACTICE:

“These preliminary data underscore the potential for the integration of hypnosis into the management of intervention-related pain in clinical care,” the authors wrote.

SOURCE:

The study was led by Begonya Alcacer-Pitarch, PhD, Leeds Institute of Rheumatic and Musculoskeletal Medicine, the University of Leeds, and Chapel Allerton Hospital in Leeds, United Kingdom. It was published as a correspondence on September 10, 2024, in The Lancet Rheumatology.

LIMITATIONS:

The small sample size may limit the generalizability of the findings. The methods used for data collection were not standardized, and the individuals included in the study may have introduced selection bias.

DISCLOSURES:

The study did not have a funding source. The authors declared no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Four triptans are more effective for acute migraine than newer, more expensive medications for this headache type, new research suggested.

Results of a large systematic review and meta-analysis showed that eletriptan, rizatriptan, sumatriptan, and zolmitriptan were more effective than lasmiditan, rimegepant, and ubrogepant, which investigators found were as effective as nonsteroidal anti-inflammatory drugs (NSAIDs).

International guidelines generally endorse NSAIDs as the first-line treatment for migraine and recommend triptans for moderate to severe episodes or when the response to NSAIDs is insufficient.

However, based on the study’s findings, these four triptans should be considered the treatment of choice for migraine, study investigator Andrea Cipriani, MD, PhD, professor of psychiatry at the University of Oxford in England and director of the Oxford Health Clinical Research Facility, told a press briefing.

The investigators added that these particular triptans should be “included in the WHO [World Health Organization] List of Essential Medicines to promote global accessibility and uniform standards of care.”

The study was published online in The BMJ.
 

Filling the Knowledge Gap

To date, almost all migraine studies have compared migraine drugs with placebo, so there’s a knowledge gap, said Dr. Cipriani. As a result, “there’s no clear consensus among experts and guidelines about which specific drug classes should be prescribed initially, and this is a clinical problem.”

The researchers pointed out that, in recent years, lasmiditan and gepants have been introduced as further treatment options, especially for patients in whom triptans are contraindicated because of their potential vasoconstrictive effects and higher risk for ischemic events.

The analysis included 137 double-blind, randomized, controlled trials that were primarily sponsored by the pharmaceutical industry. It included 89,445 adult outpatients with migraine (mean age, 40.3 years; 85.6% women).

Only drugs licensed for migraine or headache that are recommended in at least one country were included. Researchers divided these 17 drugs into five categories: Antipyretics (paracetamol), ditans (lasmiditan), gepants (rimegepant and ubrogepant), NSAIDs (acetylsalicylic acid, celecoxib, diclofenac potassium, ibuprofen, naproxen sodium, and phenazone), and triptans (almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan, and zolmitriptan).

The study’s primary outcomes were freedom from pain at 2 hours and at 2-24 hours, without the use of rescue drugs.

Investigators used sumatriptan as the reference intervention because it is the most commonly prescribed migraine drug and is included in the WHO Model Lists of Essential Medicines.

The study showed all active interventions were better than placebo for pain freedom at 2 hours; with the exception of paracetamol and naratriptan, all were better for sustained pain freedom from 2 to 24 hours.

When the active interventions were compared with each other, eletriptan outperformed other drugs for achieving pain freedom at 2 hours. It was followed by rizatriptan, sumatriptan, and zolmitriptan (odds ratio [OR], 1.35-3.01). For sustained pain freedom up to 24 hours, the most efficacious interventions were eletriptan (OR, 1.41-2.73) and ibuprofen (OR, 3.16-4.82).

As for secondary efficacy outcomes, in head-to-head comparisons, eletriptan was superior to nearly all other active interventions for pain relief at 2 hours and for the use of rescue drugs.

As for adverse events, dizziness was more commonly associated with lasmiditan, eletriptan, sumatriptan, and zolmitriptan, while fatigue and sedation occurred more frequently with eletriptan and lasmiditan. Nausea was more often associated with lasmiditan, sumatriptan, zolmitriptan, and ubrogepant. Eletriptan was the only intervention most frequently associated with chest pain or discomfort.
 

Need to Update Guidelines?

Considering the new results, Dr. Cipriani and study coauthor Messoud Ashina, MD, PhD, professor of neurology, University of Copenhagen in Denmark, said clinical guidelines for acute migraine management should be updated.

While triptans are contraindicated in patients with vascular disease, the researchers noted that “cerebrovascular events may present primarily as migraine-like headaches, and misdiagnosis of transient ischemic attack and minor stroke as migraine is not rare.”

Recently, lasmiditan, rimegepant, and ubrogepant — which are not associated with vasoconstrictive effects — have been promoted as alternatives in patients for whom triptans are contraindicated or not tolerated. But the high costs of these drugs put them out of reach for some patients, the investigators noted.

Triptans are widely underutilized, Dr. Ashina noted during the press briefing. Current use ranges from 17% to 22% in the United States and from 3% to 22.5% in Europe.

The investigators said that triptans have been shown to be superior and should be promoted globally, adding that the limited access and substantial underutilization of these medications are “missed opportunities to offer more effective treatments.”

The new results underscore the importance of head-to-head trials, which is the gold standard, said Dr. Cipriani.

The investigators noted that the study’s main limitation was the quality of the data, which was deemed to be low, or very low, for most comparisons. Other potential limitations included lack of individual patient data; exclusion of combination drugs; inclusion of only oral treatments; and not considering type of oral formulation, consistency in response across migraine episodes, or cost-effectiveness.

The study also did not cover important clinical issues that might inform treatment decision-making, including drug overuse headache or potential withdrawal symptoms. And the authors were unable to quantify some outcomes, such as global functioning.
 

‘Best Profile’?

Reached for comment, Neurologist Nina Riggins, MD, PhD, Headache Center of Excellence, Palo Alto VA Medical Center in California, praised the authors for a “great job” of bringing attention to the topic.

However, she noted that the investigators’ characterization of the four triptans as having the “best profile” for acute migraine gave her pause.

“Calling triptans the medication with the ‘best profile’ might be not applicable in many cases,” she said. For example, those who need acute medication more than two to three times a week in addition to those with cardiovascular contraindications to triptans may fall outside of that category.

Dr. Riggins said that “it makes sense” that longer-acting triptans like frovatriptan and naratriptan may not rank highly for efficacy within the first 2 hours. However, these agents likely offer a superior therapeutic profile in specific contexts, such as menstrual-related migraine.

In addition, while triptans are known to cause medication overuse headache, this may not be the case with gepants, she noted.

In a release from the Science Media Center, a nonprofit organization promoting voices and views of the scientific community, Eloísa Rubio-Beltrán, PhD, research associate with The Migraine Trust at the Wolfson Sensory, Pain and Regeneration Centre, King’s College London in England, said the findings should affect migraine treatment guidelines.

“As the study highlights, due to their high efficacy and low cost, triptans should be the first-line treatment option for the acute treatment of migraine. These results should inform treatment guidelines and support the inclusion of the best performing triptans into the List of Essential Medicines, to optimize treatment, allowing patients to access more efficacious options,” said Dr. Rubio-Beltrán.

It is also important to note that gepants and ditans were developed to offer alternatives for patients who show no improvement from triptans, she added.

She pointed out that these medications were not developed as a substitute for triptans, but rather to expand the number of treatment options for migraine.

“Nonetheless,” she added, “this study highlights the need for further research on the pathophysiology of migraine, which will allow the discovery of novel targets, and thus, novel treatments options that will benefit all patient populations.”

The study was funded by the NIHR Oxford Health Biomedical Research Centre and the Lundbeck Foundation. Dr. Cipriani reported receiving research, educational, and consultancy fees from Italian Network for Pediatric Clinical Trials, Fondazione Cariplo, Lundbeck, and Angelini Pharma. Dr. Ashina is a consultant, speaker, or scientific adviser for AbbVie, Amgen, AstraZeneca, Eli Lilly, GSK, Lundbeck, Novartis, Pfizer, and Teva; is the past president of the International Headache Society; and an associate editor of The Journal of Headache and Pain and Brain. Dr. Riggins has consulted for Gerson Lehrman Group; participated in compensated work with AcademicCME and Association of Migraine Disorders; was a principal investigator on research with electroCore, Theranica, and Eli Lilly; serves on advisory boards for Theranica, Teva, Lundbeck, Amneal Pharmaceuticals, NeurologyLive, and Miles for Migraine; and is a project advisor for Clinical Awareness Initiative with Clinical Neurological Society of America. Dr. Rubio-Beltrán reported serving as a junior editorial board member of The Journal of Headache and Pain and a junior representative of the International Headache Society; receiving research support from The Migraine Trust, Eli Lilly, CoLucid Pharmaceuticals, Amgen, Novartis, and Kallyope; and receiving travel support from CoLucid Pharmaceuticals, Allergan, and Novartis.

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

Four triptans are more effective for acute migraine than newer, more expensive medications for this headache type, new research suggested.

Results of a large systematic review and meta-analysis showed that eletriptan, rizatriptan, sumatriptan, and zolmitriptan were more effective than lasmiditan, rimegepant, and ubrogepant, which investigators found were as effective as nonsteroidal anti-inflammatory drugs (NSAIDs).

International guidelines generally endorse NSAIDs as the first-line treatment for migraine and recommend triptans for moderate to severe episodes or when the response to NSAIDs is insufficient.

However, based on the study’s findings, these four triptans should be considered the treatment of choice for migraine, study investigator Andrea Cipriani, MD, PhD, professor of psychiatry at the University of Oxford in England and director of the Oxford Health Clinical Research Facility, told a press briefing.

The investigators added that these particular triptans should be “included in the WHO [World Health Organization] List of Essential Medicines to promote global accessibility and uniform standards of care.”

The study was published online in The BMJ.
 

Filling the Knowledge Gap

To date, almost all migraine studies have compared migraine drugs with placebo, so there’s a knowledge gap, said Dr. Cipriani. As a result, “there’s no clear consensus among experts and guidelines about which specific drug classes should be prescribed initially, and this is a clinical problem.”

The researchers pointed out that, in recent years, lasmiditan and gepants have been introduced as further treatment options, especially for patients in whom triptans are contraindicated because of their potential vasoconstrictive effects and higher risk for ischemic events.

The analysis included 137 double-blind, randomized, controlled trials that were primarily sponsored by the pharmaceutical industry. It included 89,445 adult outpatients with migraine (mean age, 40.3 years; 85.6% women).

Only drugs licensed for migraine or headache that are recommended in at least one country were included. Researchers divided these 17 drugs into five categories: Antipyretics (paracetamol), ditans (lasmiditan), gepants (rimegepant and ubrogepant), NSAIDs (acetylsalicylic acid, celecoxib, diclofenac potassium, ibuprofen, naproxen sodium, and phenazone), and triptans (almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan, and zolmitriptan).

The study’s primary outcomes were freedom from pain at 2 hours and at 2-24 hours, without the use of rescue drugs.

Investigators used sumatriptan as the reference intervention because it is the most commonly prescribed migraine drug and is included in the WHO Model Lists of Essential Medicines.

The study showed all active interventions were better than placebo for pain freedom at 2 hours; with the exception of paracetamol and naratriptan, all were better for sustained pain freedom from 2 to 24 hours.

When the active interventions were compared with each other, eletriptan outperformed other drugs for achieving pain freedom at 2 hours. It was followed by rizatriptan, sumatriptan, and zolmitriptan (odds ratio [OR], 1.35-3.01). For sustained pain freedom up to 24 hours, the most efficacious interventions were eletriptan (OR, 1.41-2.73) and ibuprofen (OR, 3.16-4.82).

As for secondary efficacy outcomes, in head-to-head comparisons, eletriptan was superior to nearly all other active interventions for pain relief at 2 hours and for the use of rescue drugs.

As for adverse events, dizziness was more commonly associated with lasmiditan, eletriptan, sumatriptan, and zolmitriptan, while fatigue and sedation occurred more frequently with eletriptan and lasmiditan. Nausea was more often associated with lasmiditan, sumatriptan, zolmitriptan, and ubrogepant. Eletriptan was the only intervention most frequently associated with chest pain or discomfort.
 

Need to Update Guidelines?

Considering the new results, Dr. Cipriani and study coauthor Messoud Ashina, MD, PhD, professor of neurology, University of Copenhagen in Denmark, said clinical guidelines for acute migraine management should be updated.

While triptans are contraindicated in patients with vascular disease, the researchers noted that “cerebrovascular events may present primarily as migraine-like headaches, and misdiagnosis of transient ischemic attack and minor stroke as migraine is not rare.”

Recently, lasmiditan, rimegepant, and ubrogepant — which are not associated with vasoconstrictive effects — have been promoted as alternatives in patients for whom triptans are contraindicated or not tolerated. But the high costs of these drugs put them out of reach for some patients, the investigators noted.

Triptans are widely underutilized, Dr. Ashina noted during the press briefing. Current use ranges from 17% to 22% in the United States and from 3% to 22.5% in Europe.

The investigators said that triptans have been shown to be superior and should be promoted globally, adding that the limited access and substantial underutilization of these medications are “missed opportunities to offer more effective treatments.”

The new results underscore the importance of head-to-head trials, which is the gold standard, said Dr. Cipriani.

The investigators noted that the study’s main limitation was the quality of the data, which was deemed to be low, or very low, for most comparisons. Other potential limitations included lack of individual patient data; exclusion of combination drugs; inclusion of only oral treatments; and not considering type of oral formulation, consistency in response across migraine episodes, or cost-effectiveness.

The study also did not cover important clinical issues that might inform treatment decision-making, including drug overuse headache or potential withdrawal symptoms. And the authors were unable to quantify some outcomes, such as global functioning.
 

‘Best Profile’?

Reached for comment, Neurologist Nina Riggins, MD, PhD, Headache Center of Excellence, Palo Alto VA Medical Center in California, praised the authors for a “great job” of bringing attention to the topic.

However, she noted that the investigators’ characterization of the four triptans as having the “best profile” for acute migraine gave her pause.

“Calling triptans the medication with the ‘best profile’ might be not applicable in many cases,” she said. For example, those who need acute medication more than two to three times a week in addition to those with cardiovascular contraindications to triptans may fall outside of that category.

Dr. Riggins said that “it makes sense” that longer-acting triptans like frovatriptan and naratriptan may not rank highly for efficacy within the first 2 hours. However, these agents likely offer a superior therapeutic profile in specific contexts, such as menstrual-related migraine.

In addition, while triptans are known to cause medication overuse headache, this may not be the case with gepants, she noted.

In a release from the Science Media Center, a nonprofit organization promoting voices and views of the scientific community, Eloísa Rubio-Beltrán, PhD, research associate with The Migraine Trust at the Wolfson Sensory, Pain and Regeneration Centre, King’s College London in England, said the findings should affect migraine treatment guidelines.

“As the study highlights, due to their high efficacy and low cost, triptans should be the first-line treatment option for the acute treatment of migraine. These results should inform treatment guidelines and support the inclusion of the best performing triptans into the List of Essential Medicines, to optimize treatment, allowing patients to access more efficacious options,” said Dr. Rubio-Beltrán.

It is also important to note that gepants and ditans were developed to offer alternatives for patients who show no improvement from triptans, she added.

She pointed out that these medications were not developed as a substitute for triptans, but rather to expand the number of treatment options for migraine.

“Nonetheless,” she added, “this study highlights the need for further research on the pathophysiology of migraine, which will allow the discovery of novel targets, and thus, novel treatments options that will benefit all patient populations.”

The study was funded by the NIHR Oxford Health Biomedical Research Centre and the Lundbeck Foundation. Dr. Cipriani reported receiving research, educational, and consultancy fees from Italian Network for Pediatric Clinical Trials, Fondazione Cariplo, Lundbeck, and Angelini Pharma. Dr. Ashina is a consultant, speaker, or scientific adviser for AbbVie, Amgen, AstraZeneca, Eli Lilly, GSK, Lundbeck, Novartis, Pfizer, and Teva; is the past president of the International Headache Society; and an associate editor of The Journal of Headache and Pain and Brain. Dr. Riggins has consulted for Gerson Lehrman Group; participated in compensated work with AcademicCME and Association of Migraine Disorders; was a principal investigator on research with electroCore, Theranica, and Eli Lilly; serves on advisory boards for Theranica, Teva, Lundbeck, Amneal Pharmaceuticals, NeurologyLive, and Miles for Migraine; and is a project advisor for Clinical Awareness Initiative with Clinical Neurological Society of America. Dr. Rubio-Beltrán reported serving as a junior editorial board member of The Journal of Headache and Pain and a junior representative of the International Headache Society; receiving research support from The Migraine Trust, Eli Lilly, CoLucid Pharmaceuticals, Amgen, Novartis, and Kallyope; and receiving travel support from CoLucid Pharmaceuticals, Allergan, and Novartis.

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

Four triptans are more effective for acute migraine than newer, more expensive medications for this headache type, new research suggested.

Results of a large systematic review and meta-analysis showed that eletriptan, rizatriptan, sumatriptan, and zolmitriptan were more effective than lasmiditan, rimegepant, and ubrogepant, which investigators found were as effective as nonsteroidal anti-inflammatory drugs (NSAIDs).

International guidelines generally endorse NSAIDs as the first-line treatment for migraine and recommend triptans for moderate to severe episodes or when the response to NSAIDs is insufficient.

However, based on the study’s findings, these four triptans should be considered the treatment of choice for migraine, study investigator Andrea Cipriani, MD, PhD, professor of psychiatry at the University of Oxford in England and director of the Oxford Health Clinical Research Facility, told a press briefing.

The investigators added that these particular triptans should be “included in the WHO [World Health Organization] List of Essential Medicines to promote global accessibility and uniform standards of care.”

The study was published online in The BMJ.
 

Filling the Knowledge Gap

To date, almost all migraine studies have compared migraine drugs with placebo, so there’s a knowledge gap, said Dr. Cipriani. As a result, “there’s no clear consensus among experts and guidelines about which specific drug classes should be prescribed initially, and this is a clinical problem.”

The researchers pointed out that, in recent years, lasmiditan and gepants have been introduced as further treatment options, especially for patients in whom triptans are contraindicated because of their potential vasoconstrictive effects and higher risk for ischemic events.

The analysis included 137 double-blind, randomized, controlled trials that were primarily sponsored by the pharmaceutical industry. It included 89,445 adult outpatients with migraine (mean age, 40.3 years; 85.6% women).

Only drugs licensed for migraine or headache that are recommended in at least one country were included. Researchers divided these 17 drugs into five categories: Antipyretics (paracetamol), ditans (lasmiditan), gepants (rimegepant and ubrogepant), NSAIDs (acetylsalicylic acid, celecoxib, diclofenac potassium, ibuprofen, naproxen sodium, and phenazone), and triptans (almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan, and zolmitriptan).

The study’s primary outcomes were freedom from pain at 2 hours and at 2-24 hours, without the use of rescue drugs.

Investigators used sumatriptan as the reference intervention because it is the most commonly prescribed migraine drug and is included in the WHO Model Lists of Essential Medicines.

The study showed all active interventions were better than placebo for pain freedom at 2 hours; with the exception of paracetamol and naratriptan, all were better for sustained pain freedom from 2 to 24 hours.

When the active interventions were compared with each other, eletriptan outperformed other drugs for achieving pain freedom at 2 hours. It was followed by rizatriptan, sumatriptan, and zolmitriptan (odds ratio [OR], 1.35-3.01). For sustained pain freedom up to 24 hours, the most efficacious interventions were eletriptan (OR, 1.41-2.73) and ibuprofen (OR, 3.16-4.82).

As for secondary efficacy outcomes, in head-to-head comparisons, eletriptan was superior to nearly all other active interventions for pain relief at 2 hours and for the use of rescue drugs.

As for adverse events, dizziness was more commonly associated with lasmiditan, eletriptan, sumatriptan, and zolmitriptan, while fatigue and sedation occurred more frequently with eletriptan and lasmiditan. Nausea was more often associated with lasmiditan, sumatriptan, zolmitriptan, and ubrogepant. Eletriptan was the only intervention most frequently associated with chest pain or discomfort.
 

Need to Update Guidelines?

Considering the new results, Dr. Cipriani and study coauthor Messoud Ashina, MD, PhD, professor of neurology, University of Copenhagen in Denmark, said clinical guidelines for acute migraine management should be updated.

While triptans are contraindicated in patients with vascular disease, the researchers noted that “cerebrovascular events may present primarily as migraine-like headaches, and misdiagnosis of transient ischemic attack and minor stroke as migraine is not rare.”

Recently, lasmiditan, rimegepant, and ubrogepant — which are not associated with vasoconstrictive effects — have been promoted as alternatives in patients for whom triptans are contraindicated or not tolerated. But the high costs of these drugs put them out of reach for some patients, the investigators noted.

Triptans are widely underutilized, Dr. Ashina noted during the press briefing. Current use ranges from 17% to 22% in the United States and from 3% to 22.5% in Europe.

The investigators said that triptans have been shown to be superior and should be promoted globally, adding that the limited access and substantial underutilization of these medications are “missed opportunities to offer more effective treatments.”

The new results underscore the importance of head-to-head trials, which is the gold standard, said Dr. Cipriani.

The investigators noted that the study’s main limitation was the quality of the data, which was deemed to be low, or very low, for most comparisons. Other potential limitations included lack of individual patient data; exclusion of combination drugs; inclusion of only oral treatments; and not considering type of oral formulation, consistency in response across migraine episodes, or cost-effectiveness.

The study also did not cover important clinical issues that might inform treatment decision-making, including drug overuse headache or potential withdrawal symptoms. And the authors were unable to quantify some outcomes, such as global functioning.
 

‘Best Profile’?

Reached for comment, Neurologist Nina Riggins, MD, PhD, Headache Center of Excellence, Palo Alto VA Medical Center in California, praised the authors for a “great job” of bringing attention to the topic.

However, she noted that the investigators’ characterization of the four triptans as having the “best profile” for acute migraine gave her pause.

“Calling triptans the medication with the ‘best profile’ might be not applicable in many cases,” she said. For example, those who need acute medication more than two to three times a week in addition to those with cardiovascular contraindications to triptans may fall outside of that category.

Dr. Riggins said that “it makes sense” that longer-acting triptans like frovatriptan and naratriptan may not rank highly for efficacy within the first 2 hours. However, these agents likely offer a superior therapeutic profile in specific contexts, such as menstrual-related migraine.

In addition, while triptans are known to cause medication overuse headache, this may not be the case with gepants, she noted.

In a release from the Science Media Center, a nonprofit organization promoting voices and views of the scientific community, Eloísa Rubio-Beltrán, PhD, research associate with The Migraine Trust at the Wolfson Sensory, Pain and Regeneration Centre, King’s College London in England, said the findings should affect migraine treatment guidelines.

“As the study highlights, due to their high efficacy and low cost, triptans should be the first-line treatment option for the acute treatment of migraine. These results should inform treatment guidelines and support the inclusion of the best performing triptans into the List of Essential Medicines, to optimize treatment, allowing patients to access more efficacious options,” said Dr. Rubio-Beltrán.

It is also important to note that gepants and ditans were developed to offer alternatives for patients who show no improvement from triptans, she added.

She pointed out that these medications were not developed as a substitute for triptans, but rather to expand the number of treatment options for migraine.

“Nonetheless,” she added, “this study highlights the need for further research on the pathophysiology of migraine, which will allow the discovery of novel targets, and thus, novel treatments options that will benefit all patient populations.”

The study was funded by the NIHR Oxford Health Biomedical Research Centre and the Lundbeck Foundation. Dr. Cipriani reported receiving research, educational, and consultancy fees from Italian Network for Pediatric Clinical Trials, Fondazione Cariplo, Lundbeck, and Angelini Pharma. Dr. Ashina is a consultant, speaker, or scientific adviser for AbbVie, Amgen, AstraZeneca, Eli Lilly, GSK, Lundbeck, Novartis, Pfizer, and Teva; is the past president of the International Headache Society; and an associate editor of The Journal of Headache and Pain and Brain. Dr. Riggins has consulted for Gerson Lehrman Group; participated in compensated work with AcademicCME and Association of Migraine Disorders; was a principal investigator on research with electroCore, Theranica, and Eli Lilly; serves on advisory boards for Theranica, Teva, Lundbeck, Amneal Pharmaceuticals, NeurologyLive, and Miles for Migraine; and is a project advisor for Clinical Awareness Initiative with Clinical Neurological Society of America. Dr. Rubio-Beltrán reported serving as a junior editorial board member of The Journal of Headache and Pain and a junior representative of the International Headache Society; receiving research support from The Migraine Trust, Eli Lilly, CoLucid Pharmaceuticals, Amgen, Novartis, and Kallyope; and receiving travel support from CoLucid Pharmaceuticals, Allergan, and Novartis.

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