Women diagnosed with early-stage breast cancer are more likely to become long-term survivors of the disease now than they were 20 years ago, a new study found.

Researchers at the University of Oxford (England) conducted an observational study that examined case fatality rates for women with breast cancer and found that the prognosis for women has “improved substantially” over the past few decades. For women diagnosed with early invasive breast cancer during the 1990s, the risk of death within 5 years of diagnosis was just over 14% on average. For women diagnosed during the 2010s, it was nearly 5% on average.

“The take-home message in our study is that it’s good news for women who are diagnosed with early breast cancer today because most of them can expect to become long-term cancer survivors, and so I think our results are reassuring,” said lead study author Carolyn Taylor, DPhil, a clinical oncologist from the Nuffield Department Of Population Health, University of Oxford.

The study was published online in the BMJ.

Although breast cancer survival has improved, recent estimates don’t incorporate detailed data on age, tumor size, tumor grade, and nodal and receptor status. In the current population-based study, researchers explored improvement in survival from early-stage breast cancer. They used nine patient and tumor characteristics as factors in their analysis.

The study is based on data from the National Cancer Registration for 512,447 women in England who were diagnosed with early-stage invasive breast cancer between 1993 and 2015. Women were broken into four groups: those diagnosed during 1993-1999, 2000-2004, 2005-2009, and 2010-2015.

The study focused on women who initially underwent either breast-conserving surgery or mastectomy as their first treatment. Data included age, tumor size, tumor grade, number of positive nodes, and estrogen receptor (ER) status. For women who were diagnosed from 2010 to 2015, HER2 status was included. Data regarding recurrence, receipt of neoadjuvant therapy, and patients who were diagnosed with more than one cancer were not included.

The major finding: Among women diagnosed with early-stage invasive breast cancer, the risk of dying decreased almost threefold between 1993 and 2015. The 5-year cumulative case fatality risk was 14.4% for women diagnosed in the 1990s (1993-1999) versus 4.9% for women diagnosed about 2 decades later (2010-2015).

Dr. Taylor and colleagues found that the case fatality rate was highest during the 5 years after diagnosis; within those years, the rates typically increased during the first 2 years, peaked during the third, and declined thereafter.

The 5-year risk of death, however, varied widely among women in the population. For most (62.8%) who were diagnosed between 2010 and 2015, the case fatality risk was 3% or less; however, for a small subset of women (4.6%), the risk reached 20% or higher.

Patients with ER-negative tumors tended to have worse prognoses in the first decade following their diagnosis. Overall, higher tumor size and grade, more positive nodes, and older age tended to be associated with worse prognoses.

Overall, the annual case fatality rates decreased over time in nearly every patient group.

While Dr. Taylor said these findings are encouraging, she added that the investigators did not analyze why survival rates have improved over 2 decades.

“We didn’t explain how much of the improvement was due to advances treatments, improved screening rates, etc,” Dr. Taylor said. Another limitation is that data on recurrence were not available.

Kathy Miller, MD, who specializes in breast cancer at the Melvin and Bren Simon Cancer Center at Indiana University, Indianapolis, said the 5-year mark for survival is great news for some patients with breast cancer but that the time frame doesn’t apply to all.

While the risk of case fatality from breast cancer may be higher during the first 5 years after diagnosis, Dr. Miller said that is not the case for women with ER-positive breast cancer. In the study, the researchers highlighted this trend for ER status: before the 10-year mark, survival rates for women with ER-positive disease were better, but after the 10-year mark, those with ER-negative tumors seemed to fare slightly better.

“Many patients have heard this very arbitrary 5-year mark, and for patients with ER-positive disease, that 5-year mark has no meaning, because their risk in any given year is very low and it stays at that very low consistent level for at least 15 years, probably longer,” Dr. Miller said in an interview. “I think a better way to think about this for ER-positive patients is that every day that goes by without a problem makes it a tiny bit less likely that you will ever have a problem.”

The authors took a similar view for the overall population, concluding that, “although deaths from breast cancer will continue to occur beyond this [5-year mark], the risk during each subsequent 5-year period is likely to be lower than during the first 5 years.”

The research was funded by Cancer Research UK, the National Institute for Health Research Oxford Biomedical Research Centre, the U.K. Medical Research Council, and the University of Oxford. Some study authors received support for several of these institutions, but they reported no financial relationships with organizations that might have had an interest in the submitted work during the previous 3 years.

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

Women diagnosed with early-stage breast cancer are more likely to become long-term survivors of the disease now than they were 20 years ago, a new study found.

Researchers at the University of Oxford (England) conducted an observational study that examined case fatality rates for women with breast cancer and found that the prognosis for women has “improved substantially” over the past few decades. For women diagnosed with early invasive breast cancer during the 1990s, the risk of death within 5 years of diagnosis was just over 14% on average. For women diagnosed during the 2010s, it was nearly 5% on average.

“The take-home message in our study is that it’s good news for women who are diagnosed with early breast cancer today because most of them can expect to become long-term cancer survivors, and so I think our results are reassuring,” said lead study author Carolyn Taylor, DPhil, a clinical oncologist from the Nuffield Department Of Population Health, University of Oxford.

The study was published online in the BMJ.

Although breast cancer survival has improved, recent estimates don’t incorporate detailed data on age, tumor size, tumor grade, and nodal and receptor status. In the current population-based study, researchers explored improvement in survival from early-stage breast cancer. They used nine patient and tumor characteristics as factors in their analysis.

The study is based on data from the National Cancer Registration for 512,447 women in England who were diagnosed with early-stage invasive breast cancer between 1993 and 2015. Women were broken into four groups: those diagnosed during 1993-1999, 2000-2004, 2005-2009, and 2010-2015.

The study focused on women who initially underwent either breast-conserving surgery or mastectomy as their first treatment. Data included age, tumor size, tumor grade, number of positive nodes, and estrogen receptor (ER) status. For women who were diagnosed from 2010 to 2015, HER2 status was included. Data regarding recurrence, receipt of neoadjuvant therapy, and patients who were diagnosed with more than one cancer were not included.

The major finding: Among women diagnosed with early-stage invasive breast cancer, the risk of dying decreased almost threefold between 1993 and 2015. The 5-year cumulative case fatality risk was 14.4% for women diagnosed in the 1990s (1993-1999) versus 4.9% for women diagnosed about 2 decades later (2010-2015).

Dr. Taylor and colleagues found that the case fatality rate was highest during the 5 years after diagnosis; within those years, the rates typically increased during the first 2 years, peaked during the third, and declined thereafter.

The 5-year risk of death, however, varied widely among women in the population. For most (62.8%) who were diagnosed between 2010 and 2015, the case fatality risk was 3% or less; however, for a small subset of women (4.6%), the risk reached 20% or higher.

Patients with ER-negative tumors tended to have worse prognoses in the first decade following their diagnosis. Overall, higher tumor size and grade, more positive nodes, and older age tended to be associated with worse prognoses.

Overall, the annual case fatality rates decreased over time in nearly every patient group.

While Dr. Taylor said these findings are encouraging, she added that the investigators did not analyze why survival rates have improved over 2 decades.

“We didn’t explain how much of the improvement was due to advances treatments, improved screening rates, etc,” Dr. Taylor said. Another limitation is that data on recurrence were not available.

Kathy Miller, MD, who specializes in breast cancer at the Melvin and Bren Simon Cancer Center at Indiana University, Indianapolis, said the 5-year mark for survival is great news for some patients with breast cancer but that the time frame doesn’t apply to all.

While the risk of case fatality from breast cancer may be higher during the first 5 years after diagnosis, Dr. Miller said that is not the case for women with ER-positive breast cancer. In the study, the researchers highlighted this trend for ER status: before the 10-year mark, survival rates for women with ER-positive disease were better, but after the 10-year mark, those with ER-negative tumors seemed to fare slightly better.

“Many patients have heard this very arbitrary 5-year mark, and for patients with ER-positive disease, that 5-year mark has no meaning, because their risk in any given year is very low and it stays at that very low consistent level for at least 15 years, probably longer,” Dr. Miller said in an interview. “I think a better way to think about this for ER-positive patients is that every day that goes by without a problem makes it a tiny bit less likely that you will ever have a problem.”

The authors took a similar view for the overall population, concluding that, “although deaths from breast cancer will continue to occur beyond this [5-year mark], the risk during each subsequent 5-year period is likely to be lower than during the first 5 years.”

The research was funded by Cancer Research UK, the National Institute for Health Research Oxford Biomedical Research Centre, the U.K. Medical Research Council, and the University of Oxford. Some study authors received support for several of these institutions, but they reported no financial relationships with organizations that might have had an interest in the submitted work during the previous 3 years.

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

Women diagnosed with early-stage breast cancer are more likely to become long-term survivors of the disease now than they were 20 years ago, a new study found.

Researchers at the University of Oxford (England) conducted an observational study that examined case fatality rates for women with breast cancer and found that the prognosis for women has “improved substantially” over the past few decades. For women diagnosed with early invasive breast cancer during the 1990s, the risk of death within 5 years of diagnosis was just over 14% on average. For women diagnosed during the 2010s, it was nearly 5% on average.

“The take-home message in our study is that it’s good news for women who are diagnosed with early breast cancer today because most of them can expect to become long-term cancer survivors, and so I think our results are reassuring,” said lead study author Carolyn Taylor, DPhil, a clinical oncologist from the Nuffield Department Of Population Health, University of Oxford.

The study was published online in the BMJ.

Although breast cancer survival has improved, recent estimates don’t incorporate detailed data on age, tumor size, tumor grade, and nodal and receptor status. In the current population-based study, researchers explored improvement in survival from early-stage breast cancer. They used nine patient and tumor characteristics as factors in their analysis.

The study is based on data from the National Cancer Registration for 512,447 women in England who were diagnosed with early-stage invasive breast cancer between 1993 and 2015. Women were broken into four groups: those diagnosed during 1993-1999, 2000-2004, 2005-2009, and 2010-2015.

The study focused on women who initially underwent either breast-conserving surgery or mastectomy as their first treatment. Data included age, tumor size, tumor grade, number of positive nodes, and estrogen receptor (ER) status. For women who were diagnosed from 2010 to 2015, HER2 status was included. Data regarding recurrence, receipt of neoadjuvant therapy, and patients who were diagnosed with more than one cancer were not included.

The major finding: Among women diagnosed with early-stage invasive breast cancer, the risk of dying decreased almost threefold between 1993 and 2015. The 5-year cumulative case fatality risk was 14.4% for women diagnosed in the 1990s (1993-1999) versus 4.9% for women diagnosed about 2 decades later (2010-2015).

Dr. Taylor and colleagues found that the case fatality rate was highest during the 5 years after diagnosis; within those years, the rates typically increased during the first 2 years, peaked during the third, and declined thereafter.

The 5-year risk of death, however, varied widely among women in the population. For most (62.8%) who were diagnosed between 2010 and 2015, the case fatality risk was 3% or less; however, for a small subset of women (4.6%), the risk reached 20% or higher.

Patients with ER-negative tumors tended to have worse prognoses in the first decade following their diagnosis. Overall, higher tumor size and grade, more positive nodes, and older age tended to be associated with worse prognoses.

Overall, the annual case fatality rates decreased over time in nearly every patient group.

While Dr. Taylor said these findings are encouraging, she added that the investigators did not analyze why survival rates have improved over 2 decades.

“We didn’t explain how much of the improvement was due to advances treatments, improved screening rates, etc,” Dr. Taylor said. Another limitation is that data on recurrence were not available.

Kathy Miller, MD, who specializes in breast cancer at the Melvin and Bren Simon Cancer Center at Indiana University, Indianapolis, said the 5-year mark for survival is great news for some patients with breast cancer but that the time frame doesn’t apply to all.

While the risk of case fatality from breast cancer may be higher during the first 5 years after diagnosis, Dr. Miller said that is not the case for women with ER-positive breast cancer. In the study, the researchers highlighted this trend for ER status: before the 10-year mark, survival rates for women with ER-positive disease were better, but after the 10-year mark, those with ER-negative tumors seemed to fare slightly better.

“Many patients have heard this very arbitrary 5-year mark, and for patients with ER-positive disease, that 5-year mark has no meaning, because their risk in any given year is very low and it stays at that very low consistent level for at least 15 years, probably longer,” Dr. Miller said in an interview. “I think a better way to think about this for ER-positive patients is that every day that goes by without a problem makes it a tiny bit less likely that you will ever have a problem.”

The authors took a similar view for the overall population, concluding that, “although deaths from breast cancer will continue to occur beyond this [5-year mark], the risk during each subsequent 5-year period is likely to be lower than during the first 5 years.”

The research was funded by Cancer Research UK, the National Institute for Health Research Oxford Biomedical Research Centre, the U.K. Medical Research Council, and the University of Oxford. Some study authors received support for several of these institutions, but they reported no financial relationships with organizations that might have had an interest in the submitted work during the previous 3 years.

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

TOPLINE:

A pilot study suggests that kombucha consumption reduces blood glucose levels in adults with type 2 diabetes. The sample size was too small for statistical significance.

blanaru/iStock/Getty Images

METHODOLOGY:

• Prospective, randomized, double-blinded, crossover study at a single-center urban hospital system.
• A total of 12 participants with type 2 diabetes were randomly assigned to consume 240 mL of either a kombucha product or placebo daily with dinner for 4 weeks.
• After an 8-week washout, they were switched to the other product for another 4 weeks.
• Fasting blood glucose levels were self-determined at baseline and at 1 and 4 weeks, and questionnaires were used to assess secondary health outcomes.
• Questionnaire data were analyzed for all 12 participants, but only 7 who completed the study were included in the analysis of fasting blood glucose.

TAKEAWAY:

• Kombucha significantly lowered average fasting blood glucose levels at week 4, compared with baseline (164 vs. 116 mg/dL; P = .035), while the placebo was not associated with statistically significant change (162 vs. 141 mg/dL; P = .078).
• Among just the five participants with baseline fasting glucose > 130 mg/dL, kombucha consumption was associated with a mean fasting blood glucose decrease of 74.3 mg/dL, significantly greater than the 15.9 mg/dL drop with placebo (P = .017).
• On cultural enumeration, the kombucha contained mostly lactic acid bacteria, acetic acid bacteria, and yeast, with molds present.

IN PRACTICE:

“Kombucha is a growing part of the beverage market in the United States and the world, driven, in part, by the wide range of suggested health benefits. However, nearly all of these benefits are based on in vitro or animal studies, and human clinical trials are needed to validate biological outcomes.”

SOURCE:

The study was conducted by Chagai Mendelson, of MedStar Georgetown University Hospital, Washington, and colleagues. It was published in Frontiers in Nutrition.

LIMITATIONS:

• The number of participants was small, and attrition was high.
• Glucose levels were self-reported.
• Only one kombucha was studied.

DISCLOSURES:

One author is a cofounder of Synbiotic Health and another has a financial interest in the company. The other authors have no disclosures. Kombucha and placebo drinks were donated by Craft Kombucha, but the company did not have access to the data, and no authors have financial ties with that company.

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

TOPLINE:

A pilot study suggests that kombucha consumption reduces blood glucose levels in adults with type 2 diabetes. The sample size was too small for statistical significance.

blanaru/iStock/Getty Images

METHODOLOGY:

• Prospective, randomized, double-blinded, crossover study at a single-center urban hospital system.
• A total of 12 participants with type 2 diabetes were randomly assigned to consume 240 mL of either a kombucha product or placebo daily with dinner for 4 weeks.
• After an 8-week washout, they were switched to the other product for another 4 weeks.
• Fasting blood glucose levels were self-determined at baseline and at 1 and 4 weeks, and questionnaires were used to assess secondary health outcomes.
• Questionnaire data were analyzed for all 12 participants, but only 7 who completed the study were included in the analysis of fasting blood glucose.

TAKEAWAY:

• Kombucha significantly lowered average fasting blood glucose levels at week 4, compared with baseline (164 vs. 116 mg/dL; P = .035), while the placebo was not associated with statistically significant change (162 vs. 141 mg/dL; P = .078).
• Among just the five participants with baseline fasting glucose > 130 mg/dL, kombucha consumption was associated with a mean fasting blood glucose decrease of 74.3 mg/dL, significantly greater than the 15.9 mg/dL drop with placebo (P = .017).
• On cultural enumeration, the kombucha contained mostly lactic acid bacteria, acetic acid bacteria, and yeast, with molds present.

IN PRACTICE:

“Kombucha is a growing part of the beverage market in the United States and the world, driven, in part, by the wide range of suggested health benefits. However, nearly all of these benefits are based on in vitro or animal studies, and human clinical trials are needed to validate biological outcomes.”

SOURCE:

The study was conducted by Chagai Mendelson, of MedStar Georgetown University Hospital, Washington, and colleagues. It was published in Frontiers in Nutrition.

LIMITATIONS:

• The number of participants was small, and attrition was high.
• Glucose levels were self-reported.
• Only one kombucha was studied.

DISCLOSURES:

One author is a cofounder of Synbiotic Health and another has a financial interest in the company. The other authors have no disclosures. Kombucha and placebo drinks were donated by Craft Kombucha, but the company did not have access to the data, and no authors have financial ties with that company.

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

TOPLINE:

A pilot study suggests that kombucha consumption reduces blood glucose levels in adults with type 2 diabetes. The sample size was too small for statistical significance.

blanaru/iStock/Getty Images

METHODOLOGY:

• Prospective, randomized, double-blinded, crossover study at a single-center urban hospital system.
• A total of 12 participants with type 2 diabetes were randomly assigned to consume 240 mL of either a kombucha product or placebo daily with dinner for 4 weeks.
• After an 8-week washout, they were switched to the other product for another 4 weeks.
• Fasting blood glucose levels were self-determined at baseline and at 1 and 4 weeks, and questionnaires were used to assess secondary health outcomes.
• Questionnaire data were analyzed for all 12 participants, but only 7 who completed the study were included in the analysis of fasting blood glucose.

TAKEAWAY:

• Kombucha significantly lowered average fasting blood glucose levels at week 4, compared with baseline (164 vs. 116 mg/dL; P = .035), while the placebo was not associated with statistically significant change (162 vs. 141 mg/dL; P = .078).
• Among just the five participants with baseline fasting glucose > 130 mg/dL, kombucha consumption was associated with a mean fasting blood glucose decrease of 74.3 mg/dL, significantly greater than the 15.9 mg/dL drop with placebo (P = .017).
• On cultural enumeration, the kombucha contained mostly lactic acid bacteria, acetic acid bacteria, and yeast, with molds present.

IN PRACTICE:

“Kombucha is a growing part of the beverage market in the United States and the world, driven, in part, by the wide range of suggested health benefits. However, nearly all of these benefits are based on in vitro or animal studies, and human clinical trials are needed to validate biological outcomes.”

SOURCE:

The study was conducted by Chagai Mendelson, of MedStar Georgetown University Hospital, Washington, and colleagues. It was published in Frontiers in Nutrition.

LIMITATIONS:

• The number of participants was small, and attrition was high.
• Glucose levels were self-reported.
• Only one kombucha was studied.

DISCLOSURES:

One author is a cofounder of Synbiotic Health and another has a financial interest in the company. The other authors have no disclosures. Kombucha and placebo drinks were donated by Craft Kombucha, but the company did not have access to the data, and no authors have financial ties with that company.

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

This transcript has been edited for clarity.

When I went to med school, we were taught to take a sexual history. Do you smoke? Do you drink? Do you do drugs? Do you have sex? Men, women, or both? And that was it. We’re telling patients that sex is a vice, something that is dangerous and that you should feel bad about. But sex is how we’re all here and how we even continue as a species. We must get comfortable as doctors talking to our patients about sexual medicine.

What if we move away from sex being in the vice category – the part of the social history that’s the bad stuff you shouldn’t be doing? Maybe we should bring it into the review of systems.

As a very basic first step, I like to ask patients four things. As a sexual medicine doctor, I deal with these four things: libido, arousal, orgasm, and pain.

Why are these important? These are the things our patients really care about; 2.3 of every 1,000 people got divorced in 2021.

Libido. Women who have distressing low sexual desire have sex on average two and a half times per month. We call this mercy sex or duty sex. I don’t know what the half time per month looks like, but people genuinely care about desire and their doctors don’t really know that.

We have a biopsychosocial toolbox to help our patients. Let me give you an example: Antidepressants can have sexual side effects. Could there be medications in our toolbox that can help our patients? Of course there can, and there are. What about education or talk therapy? We should be asking our patients what they care about and why they care about it so we can help them achieve their quality-of-life goals.

Arousal. What about arousal? Did you know that erections are a marker of cardiovascular disease in men? We know this to be true for men, and I’m certain the research would be no different for women. We know that there are many biological causes for decrease in arousal, including sleep apnea, diabetes, hypertension, and smoking. I can convince a lot of men to quit smoking because I tell them it’s bad for their penis. We have to understand what our patients care about and then advise them on why we think we can help improve these issues.

Orgasm. How about orgasm? Have you ever been asked whether you can orgasm? Have you ever been asked whether you have questions about orgasm? About 15%-20% of women report having an orgasm disorder, and we rarely talk about this in an exam room. I’ve certainly never been asked, and everybody knows what I do for a living. Not to mention all the men that I and my colleagues see who have really distressing premature ejaculation or delayed orgasm. This is pathophysiology at its finest and most complex. It is so interesting, and we have so much to learn and understand about orgasm in general.

Pain. Finally, ask about pain. It seems obvious that we should be asking our patients about their pain, which includes pelvic pain, but oftentimes we avoid talking about private parts. Pain affects not just our patients, but also their partners and their families, when our patients can’t sit without discomfort, if they can’t go and perform the daily activities that bring them joy and belonging. We have to really work with our toolbox in a biopsychosocial manner to help our patients. I often use the incredible rehabilitation specialists called pelvic floor physical therapists.

Remember, we’re talking about libido, arousal, orgasm, and pain. Sex is important to us as a species. It’s important to our patients. Please consider enhancing your sexual history–taking skills and ask patients about their desire, arousal, orgasm, and pain. Ask nonjudgmental and open-ended questions. You actually may be the only doctor to ever do so.

Dr. Rubin is an assistant clinical professor, department of urology, Georgetown University, Washington. She reported conflicts of interest with Sprout, Maternal Medical, Absorption Pharmaceuticals, GSK, and Endo.

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

This transcript has been edited for clarity.

When I went to med school, we were taught to take a sexual history. Do you smoke? Do you drink? Do you do drugs? Do you have sex? Men, women, or both? And that was it. We’re telling patients that sex is a vice, something that is dangerous and that you should feel bad about. But sex is how we’re all here and how we even continue as a species. We must get comfortable as doctors talking to our patients about sexual medicine.

What if we move away from sex being in the vice category – the part of the social history that’s the bad stuff you shouldn’t be doing? Maybe we should bring it into the review of systems.

As a very basic first step, I like to ask patients four things. As a sexual medicine doctor, I deal with these four things: libido, arousal, orgasm, and pain.

Why are these important? These are the things our patients really care about; 2.3 of every 1,000 people got divorced in 2021.

Libido. Women who have distressing low sexual desire have sex on average two and a half times per month. We call this mercy sex or duty sex. I don’t know what the half time per month looks like, but people genuinely care about desire and their doctors don’t really know that.

We have a biopsychosocial toolbox to help our patients. Let me give you an example: Antidepressants can have sexual side effects. Could there be medications in our toolbox that can help our patients? Of course there can, and there are. What about education or talk therapy? We should be asking our patients what they care about and why they care about it so we can help them achieve their quality-of-life goals.

Arousal. What about arousal? Did you know that erections are a marker of cardiovascular disease in men? We know this to be true for men, and I’m certain the research would be no different for women. We know that there are many biological causes for decrease in arousal, including sleep apnea, diabetes, hypertension, and smoking. I can convince a lot of men to quit smoking because I tell them it’s bad for their penis. We have to understand what our patients care about and then advise them on why we think we can help improve these issues.

Orgasm. How about orgasm? Have you ever been asked whether you can orgasm? Have you ever been asked whether you have questions about orgasm? About 15%-20% of women report having an orgasm disorder, and we rarely talk about this in an exam room. I’ve certainly never been asked, and everybody knows what I do for a living. Not to mention all the men that I and my colleagues see who have really distressing premature ejaculation or delayed orgasm. This is pathophysiology at its finest and most complex. It is so interesting, and we have so much to learn and understand about orgasm in general.

Pain. Finally, ask about pain. It seems obvious that we should be asking our patients about their pain, which includes pelvic pain, but oftentimes we avoid talking about private parts. Pain affects not just our patients, but also their partners and their families, when our patients can’t sit without discomfort, if they can’t go and perform the daily activities that bring them joy and belonging. We have to really work with our toolbox in a biopsychosocial manner to help our patients. I often use the incredible rehabilitation specialists called pelvic floor physical therapists.

Remember, we’re talking about libido, arousal, orgasm, and pain. Sex is important to us as a species. It’s important to our patients. Please consider enhancing your sexual history–taking skills and ask patients about their desire, arousal, orgasm, and pain. Ask nonjudgmental and open-ended questions. You actually may be the only doctor to ever do so.

Dr. Rubin is an assistant clinical professor, department of urology, Georgetown University, Washington. She reported conflicts of interest with Sprout, Maternal Medical, Absorption Pharmaceuticals, GSK, and Endo.

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

This transcript has been edited for clarity.

When I went to med school, we were taught to take a sexual history. Do you smoke? Do you drink? Do you do drugs? Do you have sex? Men, women, or both? And that was it. We’re telling patients that sex is a vice, something that is dangerous and that you should feel bad about. But sex is how we’re all here and how we even continue as a species. We must get comfortable as doctors talking to our patients about sexual medicine.

What if we move away from sex being in the vice category – the part of the social history that’s the bad stuff you shouldn’t be doing? Maybe we should bring it into the review of systems.

As a very basic first step, I like to ask patients four things. As a sexual medicine doctor, I deal with these four things: libido, arousal, orgasm, and pain.

Why are these important? These are the things our patients really care about; 2.3 of every 1,000 people got divorced in 2021.

Libido. Women who have distressing low sexual desire have sex on average two and a half times per month. We call this mercy sex or duty sex. I don’t know what the half time per month looks like, but people genuinely care about desire and their doctors don’t really know that.

We have a biopsychosocial toolbox to help our patients. Let me give you an example: Antidepressants can have sexual side effects. Could there be medications in our toolbox that can help our patients? Of course there can, and there are. What about education or talk therapy? We should be asking our patients what they care about and why they care about it so we can help them achieve their quality-of-life goals.

Arousal. What about arousal? Did you know that erections are a marker of cardiovascular disease in men? We know this to be true for men, and I’m certain the research would be no different for women. We know that there are many biological causes for decrease in arousal, including sleep apnea, diabetes, hypertension, and smoking. I can convince a lot of men to quit smoking because I tell them it’s bad for their penis. We have to understand what our patients care about and then advise them on why we think we can help improve these issues.

Orgasm. How about orgasm? Have you ever been asked whether you can orgasm? Have you ever been asked whether you have questions about orgasm? About 15%-20% of women report having an orgasm disorder, and we rarely talk about this in an exam room. I’ve certainly never been asked, and everybody knows what I do for a living. Not to mention all the men that I and my colleagues see who have really distressing premature ejaculation or delayed orgasm. This is pathophysiology at its finest and most complex. It is so interesting, and we have so much to learn and understand about orgasm in general.

Pain. Finally, ask about pain. It seems obvious that we should be asking our patients about their pain, which includes pelvic pain, but oftentimes we avoid talking about private parts. Pain affects not just our patients, but also their partners and their families, when our patients can’t sit without discomfort, if they can’t go and perform the daily activities that bring them joy and belonging. We have to really work with our toolbox in a biopsychosocial manner to help our patients. I often use the incredible rehabilitation specialists called pelvic floor physical therapists.

Remember, we’re talking about libido, arousal, orgasm, and pain. Sex is important to us as a species. It’s important to our patients. Please consider enhancing your sexual history–taking skills and ask patients about their desire, arousal, orgasm, and pain. Ask nonjudgmental and open-ended questions. You actually may be the only doctor to ever do so.

Dr. Rubin is an assistant clinical professor, department of urology, Georgetown University, Washington. She reported conflicts of interest with Sprout, Maternal Medical, Absorption Pharmaceuticals, GSK, and Endo.

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

This transcript has been edited for clarity.

Clostridioides difficile is a toxin-based infection that takes up residence in the colon due to disturbed normal bowel flora, usually after antibiotics.

Recurrent C. difficile can happen in up to a quarter of patients who receive oral vancomycin as a treatment for their infection. It can also occur with treatment with the newer agent, fidaxomicin, although possibly in fewer patients. In general, relapses are indeed common.

When I trained at Johns Hopkins under John Bartlett, he took the approach that after the second – and always after the third – relapse, an extended course of oral therapy with vancomycin could help get patients out of trouble. He used the so-called extended pulse method, where patients would take the drug for approximately 4-6 weeks and gradually reduce the dose.

This approach can also be done with fidaxomicin. However, I’m not sure it works much better than vancomycin, and there are often hurdles to using fidaxomicin because of insurers not approving it because of the expense.

What other therapies are there?

There is bezlotoxumab, which is a human monoclonal antibody targeting C. difficile toxin B. I’ve used it a few times. It is given as a one-time infusion, and there are challenges regarding cost, the logistics of setting up the infusion, and insurance approval.
 

Fecal microbiota transplant

In recent years, fecal microbiota transplants (FMT) have received a lot of attention as a different avenue of treatment that could lower the potential for relapses, with success rates usually around 80%-90%. However, in the past few years, there have been some serious safety signals because of possible transmission of dangerous pathogens, often with drug resistance, with FMT.

I’m therefore pleased to say that newer fecal microbiota products are coming in fast and furious. I thought I’d spend a few minutes speaking about these.

OpenBiome, an organization dedicated to microbiome research, offers an investigational product from screened donors that has not received Food and Drug Administration approval. It’s been around for some time. It can be used in either upper or lower GI applications, and the organization cites about an 84% success rate using this product.

There are also two new FDA-approved products I think are worth knowing about. They’ve just been approved recently and we’re a little uncertain of where they’re going to end up in the treatment landscape.

The first is from Ferring, and it goes by fecal microbiota, live-jslm (Rebyota). This is a product from qualified and screened donors, the main component of which is Bacteroides, which is given as a single dose by enema.

The company did a phase 3 trial with a Bayesian primary analysis, which I think convinced the FDA to approve this product. The success rate in people with multiple relapses was 70.6%, compared with 57.5% with placebo. The estimated treatment effect was 13.1%. Of those who did respond, over 90% were kept free of relapse over a 6-month period.

The other product, also FDA approved, is from Seres. It was previously called SER-109, and is now called fecal microbiota spores, live-brpk (Vowst). Unlike the previous product, this is orally administered, with patients taking four capsules daily for 3 days. Again, these donor-derived firmicutes have been appropriately screened and are free of potential pathogens.

The phase 3 randomized clinical trial results were published in the New England Journal of Medicine. They showed that 12% of those taking this product had a relapse, compared with 40% of those taking placebo, which is about the range we tend to see in people who have had multiple relapses. The safety profile was similar to placebo.

So, how will people use these treatments?

I think the FDA imprimatur will be attractive to people, but the products, I believe, will be priced fairly expensively, in the under $10,000 range. The first (Rebyota) is a rectal infusion; it is a one-and-done treatment but creates logistical issues. Interestingly, it could be a billable procedure for infectious disease clinicians. The ease of oral administration for Vowst, no doubt, will be very appealing. Both of these are given after completing a course of treatment with vancomycin or fidaxomicin so as not to interfere with the microbiome product.

I’ll also briefly mention a paper published in JAMA on yet another microbiome product, called VE303. This product was based on eight commensal strains of Clostridia and was given orally in a phase 2 trial. Interestingly, this worked about the same as the oral product that is already FDA approved. The study showed a recurrence rate of 13.8% in the high-dose group, compared with 45.5% in the placebo group.

I think this is exciting. Hopefully, we will have safer products that can be more reliable, although there are some concerns and logistical challenges in safely getting the products to people. And, of course, there is the expense.

But anything that can be done to help improve these patients is welcome, as once they get into the multiple-relapse phase, it is challenging to turn around. These commercialized products will hopefully become a bit more mainstream. Certainly, we’ll see how these will be utilized in the coming months and over the next few years.

Dr. Auwaerter is Clinical Director, Division of Infectious Diseases, Johns Hopkins University, Baltimore. He reported conflicts of interest with Gilead, Shionogi, and Medscape.

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

This transcript has been edited for clarity.

Clostridioides difficile is a toxin-based infection that takes up residence in the colon due to disturbed normal bowel flora, usually after antibiotics.

Recurrent C. difficile can happen in up to a quarter of patients who receive oral vancomycin as a treatment for their infection. It can also occur with treatment with the newer agent, fidaxomicin, although possibly in fewer patients. In general, relapses are indeed common.

When I trained at Johns Hopkins under John Bartlett, he took the approach that after the second – and always after the third – relapse, an extended course of oral therapy with vancomycin could help get patients out of trouble. He used the so-called extended pulse method, where patients would take the drug for approximately 4-6 weeks and gradually reduce the dose.

This approach can also be done with fidaxomicin. However, I’m not sure it works much better than vancomycin, and there are often hurdles to using fidaxomicin because of insurers not approving it because of the expense.

What other therapies are there?

There is bezlotoxumab, which is a human monoclonal antibody targeting C. difficile toxin B. I’ve used it a few times. It is given as a one-time infusion, and there are challenges regarding cost, the logistics of setting up the infusion, and insurance approval.
 

Fecal microbiota transplant

In recent years, fecal microbiota transplants (FMT) have received a lot of attention as a different avenue of treatment that could lower the potential for relapses, with success rates usually around 80%-90%. However, in the past few years, there have been some serious safety signals because of possible transmission of dangerous pathogens, often with drug resistance, with FMT.

I’m therefore pleased to say that newer fecal microbiota products are coming in fast and furious. I thought I’d spend a few minutes speaking about these.

OpenBiome, an organization dedicated to microbiome research, offers an investigational product from screened donors that has not received Food and Drug Administration approval. It’s been around for some time. It can be used in either upper or lower GI applications, and the organization cites about an 84% success rate using this product.

There are also two new FDA-approved products I think are worth knowing about. They’ve just been approved recently and we’re a little uncertain of where they’re going to end up in the treatment landscape.

The first is from Ferring, and it goes by fecal microbiota, live-jslm (Rebyota). This is a product from qualified and screened donors, the main component of which is Bacteroides, which is given as a single dose by enema.

The company did a phase 3 trial with a Bayesian primary analysis, which I think convinced the FDA to approve this product. The success rate in people with multiple relapses was 70.6%, compared with 57.5% with placebo. The estimated treatment effect was 13.1%. Of those who did respond, over 90% were kept free of relapse over a 6-month period.

The other product, also FDA approved, is from Seres. It was previously called SER-109, and is now called fecal microbiota spores, live-brpk (Vowst). Unlike the previous product, this is orally administered, with patients taking four capsules daily for 3 days. Again, these donor-derived firmicutes have been appropriately screened and are free of potential pathogens.

The phase 3 randomized clinical trial results were published in the New England Journal of Medicine. They showed that 12% of those taking this product had a relapse, compared with 40% of those taking placebo, which is about the range we tend to see in people who have had multiple relapses. The safety profile was similar to placebo.

So, how will people use these treatments?

I think the FDA imprimatur will be attractive to people, but the products, I believe, will be priced fairly expensively, in the under $10,000 range. The first (Rebyota) is a rectal infusion; it is a one-and-done treatment but creates logistical issues. Interestingly, it could be a billable procedure for infectious disease clinicians. The ease of oral administration for Vowst, no doubt, will be very appealing. Both of these are given after completing a course of treatment with vancomycin or fidaxomicin so as not to interfere with the microbiome product.

I’ll also briefly mention a paper published in JAMA on yet another microbiome product, called VE303. This product was based on eight commensal strains of Clostridia and was given orally in a phase 2 trial. Interestingly, this worked about the same as the oral product that is already FDA approved. The study showed a recurrence rate of 13.8% in the high-dose group, compared with 45.5% in the placebo group.

I think this is exciting. Hopefully, we will have safer products that can be more reliable, although there are some concerns and logistical challenges in safely getting the products to people. And, of course, there is the expense.

But anything that can be done to help improve these patients is welcome, as once they get into the multiple-relapse phase, it is challenging to turn around. These commercialized products will hopefully become a bit more mainstream. Certainly, we’ll see how these will be utilized in the coming months and over the next few years.

Dr. Auwaerter is Clinical Director, Division of Infectious Diseases, Johns Hopkins University, Baltimore. He reported conflicts of interest with Gilead, Shionogi, and Medscape.

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

This transcript has been edited for clarity.

Clostridioides difficile is a toxin-based infection that takes up residence in the colon due to disturbed normal bowel flora, usually after antibiotics.

Recurrent C. difficile can happen in up to a quarter of patients who receive oral vancomycin as a treatment for their infection. It can also occur with treatment with the newer agent, fidaxomicin, although possibly in fewer patients. In general, relapses are indeed common.

When I trained at Johns Hopkins under John Bartlett, he took the approach that after the second – and always after the third – relapse, an extended course of oral therapy with vancomycin could help get patients out of trouble. He used the so-called extended pulse method, where patients would take the drug for approximately 4-6 weeks and gradually reduce the dose.

This approach can also be done with fidaxomicin. However, I’m not sure it works much better than vancomycin, and there are often hurdles to using fidaxomicin because of insurers not approving it because of the expense.

What other therapies are there?

There is bezlotoxumab, which is a human monoclonal antibody targeting C. difficile toxin B. I’ve used it a few times. It is given as a one-time infusion, and there are challenges regarding cost, the logistics of setting up the infusion, and insurance approval.
 

Fecal microbiota transplant

In recent years, fecal microbiota transplants (FMT) have received a lot of attention as a different avenue of treatment that could lower the potential for relapses, with success rates usually around 80%-90%. However, in the past few years, there have been some serious safety signals because of possible transmission of dangerous pathogens, often with drug resistance, with FMT.

I’m therefore pleased to say that newer fecal microbiota products are coming in fast and furious. I thought I’d spend a few minutes speaking about these.

OpenBiome, an organization dedicated to microbiome research, offers an investigational product from screened donors that has not received Food and Drug Administration approval. It’s been around for some time. It can be used in either upper or lower GI applications, and the organization cites about an 84% success rate using this product.

There are also two new FDA-approved products I think are worth knowing about. They’ve just been approved recently and we’re a little uncertain of where they’re going to end up in the treatment landscape.

The first is from Ferring, and it goes by fecal microbiota, live-jslm (Rebyota). This is a product from qualified and screened donors, the main component of which is Bacteroides, which is given as a single dose by enema.

The company did a phase 3 trial with a Bayesian primary analysis, which I think convinced the FDA to approve this product. The success rate in people with multiple relapses was 70.6%, compared with 57.5% with placebo. The estimated treatment effect was 13.1%. Of those who did respond, over 90% were kept free of relapse over a 6-month period.

The other product, also FDA approved, is from Seres. It was previously called SER-109, and is now called fecal microbiota spores, live-brpk (Vowst). Unlike the previous product, this is orally administered, with patients taking four capsules daily for 3 days. Again, these donor-derived firmicutes have been appropriately screened and are free of potential pathogens.

The phase 3 randomized clinical trial results were published in the New England Journal of Medicine. They showed that 12% of those taking this product had a relapse, compared with 40% of those taking placebo, which is about the range we tend to see in people who have had multiple relapses. The safety profile was similar to placebo.

So, how will people use these treatments?

I think the FDA imprimatur will be attractive to people, but the products, I believe, will be priced fairly expensively, in the under $10,000 range. The first (Rebyota) is a rectal infusion; it is a one-and-done treatment but creates logistical issues. Interestingly, it could be a billable procedure for infectious disease clinicians. The ease of oral administration for Vowst, no doubt, will be very appealing. Both of these are given after completing a course of treatment with vancomycin or fidaxomicin so as not to interfere with the microbiome product.

I’ll also briefly mention a paper published in JAMA on yet another microbiome product, called VE303. This product was based on eight commensal strains of Clostridia and was given orally in a phase 2 trial. Interestingly, this worked about the same as the oral product that is already FDA approved. The study showed a recurrence rate of 13.8% in the high-dose group, compared with 45.5% in the placebo group.

I think this is exciting. Hopefully, we will have safer products that can be more reliable, although there are some concerns and logistical challenges in safely getting the products to people. And, of course, there is the expense.

But anything that can be done to help improve these patients is welcome, as once they get into the multiple-relapse phase, it is challenging to turn around. These commercialized products will hopefully become a bit more mainstream. Certainly, we’ll see how these will be utilized in the coming months and over the next few years.

Dr. Auwaerter is Clinical Director, Division of Infectious Diseases, Johns Hopkins University, Baltimore. He reported conflicts of interest with Gilead, Shionogi, and Medscape.

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

The U.S. Food and Drug Administration today cleared an artificial intelligence (AI)-assisted colonoscopy device called the MAGENTIQ-COLO, according to the Israeli-based manufacturer of the same name.

The device helps identify lesions in real time and is associated with a significant increase in the adenoma detection rate (ADR), according to the press release.

The device was cleared under the FDA’s 510(k) process, and follows the European CE Mark and Israel AMAR approval, which were received in mid-2021. It will be available in the United States in the coming weeks.

In a study performed in 2022 with 29 endoscopy experts and more than 950 patients, the device was validated as “one of the best-performing AI solutions in the category, increasing ADR by 26% relatively (7% in absolute values), which translated into a 21% decrease in colorectal cancer occurrence and a 35% decrease in patient mortality,” according to the press release.

In this multicenter, randomized, controlled trial conducted at 10 hospitals in Europe, the United States, and Israel, and presented at United European Gastroenterology Week 2022, the authors noted that “apart from diminutive lesions, [MAGENTIQ-COLO] increased the detection of 6- to 9-mm adenomas, suggesting that this novel [computer-aided polyp detection] system is also able to detect more clinically relevant lesions.”

The device “takes the video out of the colonoscopy device, breaks it into frames, and analyzes them in real time with its AI engine to detect polyps in them,” Dror Zur, founder and CEO of MAGENTIQ-EYE, explained in an interview. “If a polyp is detected, then MAGENTIQ-COLO signs it with a bounding box on the video’s overlay and sends it as a video with an overlay to the display monitor so the doctor can look at it and find more polyps.”

As previously reported by this news organization, research has shown that conventional colonoscopies miss about a quarter of adenomas. Many AI systems have recently come on the market, promising to improve detection by overcoming human error in detecting polyps.

Colonoscopy has become standard in most developed countries, with 15-20 million procedures performed every year in the United States alone; however, high missed rates and undetected adenomas during the procedures mean that even patients who get regular, recommended screenings are still at risk of developing colon cancer, notes the press release.

“A missed polyp can lead to interval cancer, which accounts for approximately 8%-10% of all CRC in the U.S., translated to over 13,500 cancer cases that could be prevented every year with better detection,” the press release also states.

According to the National Institutes of Health, colorectal cancer is the third leading cause of cancer-related death in the United States.

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

The U.S. Food and Drug Administration today cleared an artificial intelligence (AI)-assisted colonoscopy device called the MAGENTIQ-COLO, according to the Israeli-based manufacturer of the same name.

The device helps identify lesions in real time and is associated with a significant increase in the adenoma detection rate (ADR), according to the press release.

The device was cleared under the FDA’s 510(k) process, and follows the European CE Mark and Israel AMAR approval, which were received in mid-2021. It will be available in the United States in the coming weeks.

In a study performed in 2022 with 29 endoscopy experts and more than 950 patients, the device was validated as “one of the best-performing AI solutions in the category, increasing ADR by 26% relatively (7% in absolute values), which translated into a 21% decrease in colorectal cancer occurrence and a 35% decrease in patient mortality,” according to the press release.

In this multicenter, randomized, controlled trial conducted at 10 hospitals in Europe, the United States, and Israel, and presented at United European Gastroenterology Week 2022, the authors noted that “apart from diminutive lesions, [MAGENTIQ-COLO] increased the detection of 6- to 9-mm adenomas, suggesting that this novel [computer-aided polyp detection] system is also able to detect more clinically relevant lesions.”

The device “takes the video out of the colonoscopy device, breaks it into frames, and analyzes them in real time with its AI engine to detect polyps in them,” Dror Zur, founder and CEO of MAGENTIQ-EYE, explained in an interview. “If a polyp is detected, then MAGENTIQ-COLO signs it with a bounding box on the video’s overlay and sends it as a video with an overlay to the display monitor so the doctor can look at it and find more polyps.”

As previously reported by this news organization, research has shown that conventional colonoscopies miss about a quarter of adenomas. Many AI systems have recently come on the market, promising to improve detection by overcoming human error in detecting polyps.

Colonoscopy has become standard in most developed countries, with 15-20 million procedures performed every year in the United States alone; however, high missed rates and undetected adenomas during the procedures mean that even patients who get regular, recommended screenings are still at risk of developing colon cancer, notes the press release.

“A missed polyp can lead to interval cancer, which accounts for approximately 8%-10% of all CRC in the U.S., translated to over 13,500 cancer cases that could be prevented every year with better detection,” the press release also states.

According to the National Institutes of Health, colorectal cancer is the third leading cause of cancer-related death in the United States.

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

The U.S. Food and Drug Administration today cleared an artificial intelligence (AI)-assisted colonoscopy device called the MAGENTIQ-COLO, according to the Israeli-based manufacturer of the same name.

The device helps identify lesions in real time and is associated with a significant increase in the adenoma detection rate (ADR), according to the press release.

The device was cleared under the FDA’s 510(k) process, and follows the European CE Mark and Israel AMAR approval, which were received in mid-2021. It will be available in the United States in the coming weeks.

In a study performed in 2022 with 29 endoscopy experts and more than 950 patients, the device was validated as “one of the best-performing AI solutions in the category, increasing ADR by 26% relatively (7% in absolute values), which translated into a 21% decrease in colorectal cancer occurrence and a 35% decrease in patient mortality,” according to the press release.

In this multicenter, randomized, controlled trial conducted at 10 hospitals in Europe, the United States, and Israel, and presented at United European Gastroenterology Week 2022, the authors noted that “apart from diminutive lesions, [MAGENTIQ-COLO] increased the detection of 6- to 9-mm adenomas, suggesting that this novel [computer-aided polyp detection] system is also able to detect more clinically relevant lesions.”

The device “takes the video out of the colonoscopy device, breaks it into frames, and analyzes them in real time with its AI engine to detect polyps in them,” Dror Zur, founder and CEO of MAGENTIQ-EYE, explained in an interview. “If a polyp is detected, then MAGENTIQ-COLO signs it with a bounding box on the video’s overlay and sends it as a video with an overlay to the display monitor so the doctor can look at it and find more polyps.”

As previously reported by this news organization, research has shown that conventional colonoscopies miss about a quarter of adenomas. Many AI systems have recently come on the market, promising to improve detection by overcoming human error in detecting polyps.

Colonoscopy has become standard in most developed countries, with 15-20 million procedures performed every year in the United States alone; however, high missed rates and undetected adenomas during the procedures mean that even patients who get regular, recommended screenings are still at risk of developing colon cancer, notes the press release.

“A missed polyp can lead to interval cancer, which accounts for approximately 8%-10% of all CRC in the U.S., translated to over 13,500 cancer cases that could be prevented every year with better detection,” the press release also states.

According to the National Institutes of Health, colorectal cancer is the third leading cause of cancer-related death in the United States.

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

Clinics have been coming up with new ways to add injections to their offerings ever since a new long-acting formulation of cabotegravir has been available to treat people with HIV.

At the Whitman-Walker Health Center, Washington, community health workers see about 3,200 antiretroviral users a year. With long-acting injections now available, the clinic opted to integrate the new medications into its peer staff program.

“Our peer workers are very competent,” said Rupa Patel, MD, MPH, medical liason of the pre-exposure prophylaxis for HIV prevention program at Washington University at St. Louis.* “They do phlebotomy, they give you your meds. They’re your main doctor until you really need to see the doctor.”

In the peer staff program, workers are trained in a 4-month medical residency–style program that shows them how to test for HIV, inject long-acting formulations of new drugs, and conduct follow-up visits.

Presenting the new approach at the International AIDS Society Conference on HIV Science, Dr. Patel reported that 139 people have received long-acting injections at the clinic since the program launched with a total of 314 injections administered.

The training program includes lectures, mock injection, and client care sessions, observation and supervised administration, a written exam, and case review sessions.

Retention for the second injection was 95%, with 91% of injections given within the 14-day window. For the third injection, retention was 91%, with 63% given within the window.

The program reports a high level of client satisfaction with the peer-administered injections, which are also given in a room decorated with a beach theme and music to help calm people who might be nervous of receiving shots.

“Our retention is going to be the highest compared to other clinics because your peer, your friend, is reminding you and comforting you and telling you: ‘Don’t worry, I’m on the injection too,’ ” Dr. Patel said.

Andrew Grulich, MD, PhD, head of the HIV epidemiology and prevention program at the Kirby Institute, Sydney, pointed out there is tension between wanting to use long-acting injectables for people who are struggling with taking oral therapies daily and the need to ensure that they come back for their injections on time.

“I think it’s a potential way forward – we’re learning as we’re going with these new forms of therapy,” he said in an interview. “It is absolutely critical that people turn up on time for those injections, and if they don’t, resistance can be an issue.”

Presenting new data from another project at the HIV Clinic at San Francisco General Hospital, Monica Gandhi, MD, MPH, told the conference: “There are multiple reasons why it’s hard to take oral antiretrovirals every day.”

At the HIV Clinic in San Francisco General, people without homes, those with mental illness, and those using stimulants receive care.

The clinical trials for long-acting injectable antiretrovirals included only people who were virologically suppressed, which is also the Food and Drug Administration criteria for use. However, this clinic offered long-acting injections to patients with viremia because it was too difficult for them to take a daily pill.

In a comment, Dr. Gandhi, director of the University of California, San Francisco’s Center for AIDS Research, said: “We don’t call people hard to reach, we call them hardly reached because it’s not their fault.” There are just all of these issues that have made it harder for them to take medication consistently.

Dr. Gandhi reported that, of the 133 people being treated with long-acting injectable cabotegravir and rilpivirine at the clinic through this program, 57 had viremia at baseline.

However, only two of these patients experienced virologic failure while on the injectable antiretroviral program. The overall virologic failure rate was 1.5%, which was equivalent to that seen in clinical trials in virologically suppressed individuals.

The results presented at the conference and were also published in Annals of Internal Medicine.

The clinic found that 73% of people attended their injection appointments on time, and those who did not were followed up with telephone calls to ensure they received their injection within the 14-day window.

Dr. Gandhi said people were highly motivated to turn up for their injection appointments. “They are virologically suppressed, so it feels so amazing. They’re self-motivated for the first time to want to get an injection.”

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

*Correction, 8/4/23: An earlier version of this article misstated Dr. Patel's university affiliation.

Clinics have been coming up with new ways to add injections to their offerings ever since a new long-acting formulation of cabotegravir has been available to treat people with HIV.

At the Whitman-Walker Health Center, Washington, community health workers see about 3,200 antiretroviral users a year. With long-acting injections now available, the clinic opted to integrate the new medications into its peer staff program.

“Our peer workers are very competent,” said Rupa Patel, MD, MPH, medical liason of the pre-exposure prophylaxis for HIV prevention program at Washington University at St. Louis.* “They do phlebotomy, they give you your meds. They’re your main doctor until you really need to see the doctor.”

In the peer staff program, workers are trained in a 4-month medical residency–style program that shows them how to test for HIV, inject long-acting formulations of new drugs, and conduct follow-up visits.

Presenting the new approach at the International AIDS Society Conference on HIV Science, Dr. Patel reported that 139 people have received long-acting injections at the clinic since the program launched with a total of 314 injections administered.

The training program includes lectures, mock injection, and client care sessions, observation and supervised administration, a written exam, and case review sessions.

Retention for the second injection was 95%, with 91% of injections given within the 14-day window. For the third injection, retention was 91%, with 63% given within the window.

The program reports a high level of client satisfaction with the peer-administered injections, which are also given in a room decorated with a beach theme and music to help calm people who might be nervous of receiving shots.

“Our retention is going to be the highest compared to other clinics because your peer, your friend, is reminding you and comforting you and telling you: ‘Don’t worry, I’m on the injection too,’ ” Dr. Patel said.

Andrew Grulich, MD, PhD, head of the HIV epidemiology and prevention program at the Kirby Institute, Sydney, pointed out there is tension between wanting to use long-acting injectables for people who are struggling with taking oral therapies daily and the need to ensure that they come back for their injections on time.

“I think it’s a potential way forward – we’re learning as we’re going with these new forms of therapy,” he said in an interview. “It is absolutely critical that people turn up on time for those injections, and if they don’t, resistance can be an issue.”

Presenting new data from another project at the HIV Clinic at San Francisco General Hospital, Monica Gandhi, MD, MPH, told the conference: “There are multiple reasons why it’s hard to take oral antiretrovirals every day.”

At the HIV Clinic in San Francisco General, people without homes, those with mental illness, and those using stimulants receive care.

The clinical trials for long-acting injectable antiretrovirals included only people who were virologically suppressed, which is also the Food and Drug Administration criteria for use. However, this clinic offered long-acting injections to patients with viremia because it was too difficult for them to take a daily pill.

In a comment, Dr. Gandhi, director of the University of California, San Francisco’s Center for AIDS Research, said: “We don’t call people hard to reach, we call them hardly reached because it’s not their fault.” There are just all of these issues that have made it harder for them to take medication consistently.

Dr. Gandhi reported that, of the 133 people being treated with long-acting injectable cabotegravir and rilpivirine at the clinic through this program, 57 had viremia at baseline.

However, only two of these patients experienced virologic failure while on the injectable antiretroviral program. The overall virologic failure rate was 1.5%, which was equivalent to that seen in clinical trials in virologically suppressed individuals.

The results presented at the conference and were also published in Annals of Internal Medicine.

The clinic found that 73% of people attended their injection appointments on time, and those who did not were followed up with telephone calls to ensure they received their injection within the 14-day window.

Dr. Gandhi said people were highly motivated to turn up for their injection appointments. “They are virologically suppressed, so it feels so amazing. They’re self-motivated for the first time to want to get an injection.”

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

*Correction, 8/4/23: An earlier version of this article misstated Dr. Patel's university affiliation.

Clinics have been coming up with new ways to add injections to their offerings ever since a new long-acting formulation of cabotegravir has been available to treat people with HIV.

At the Whitman-Walker Health Center, Washington, community health workers see about 3,200 antiretroviral users a year. With long-acting injections now available, the clinic opted to integrate the new medications into its peer staff program.

“Our peer workers are very competent,” said Rupa Patel, MD, MPH, medical liason of the pre-exposure prophylaxis for HIV prevention program at Washington University at St. Louis.* “They do phlebotomy, they give you your meds. They’re your main doctor until you really need to see the doctor.”

In the peer staff program, workers are trained in a 4-month medical residency–style program that shows them how to test for HIV, inject long-acting formulations of new drugs, and conduct follow-up visits.

Presenting the new approach at the International AIDS Society Conference on HIV Science, Dr. Patel reported that 139 people have received long-acting injections at the clinic since the program launched with a total of 314 injections administered.

The training program includes lectures, mock injection, and client care sessions, observation and supervised administration, a written exam, and case review sessions.

Retention for the second injection was 95%, with 91% of injections given within the 14-day window. For the third injection, retention was 91%, with 63% given within the window.

The program reports a high level of client satisfaction with the peer-administered injections, which are also given in a room decorated with a beach theme and music to help calm people who might be nervous of receiving shots.

“Our retention is going to be the highest compared to other clinics because your peer, your friend, is reminding you and comforting you and telling you: ‘Don’t worry, I’m on the injection too,’ ” Dr. Patel said.

Andrew Grulich, MD, PhD, head of the HIV epidemiology and prevention program at the Kirby Institute, Sydney, pointed out there is tension between wanting to use long-acting injectables for people who are struggling with taking oral therapies daily and the need to ensure that they come back for their injections on time.

“I think it’s a potential way forward – we’re learning as we’re going with these new forms of therapy,” he said in an interview. “It is absolutely critical that people turn up on time for those injections, and if they don’t, resistance can be an issue.”

Presenting new data from another project at the HIV Clinic at San Francisco General Hospital, Monica Gandhi, MD, MPH, told the conference: “There are multiple reasons why it’s hard to take oral antiretrovirals every day.”

At the HIV Clinic in San Francisco General, people without homes, those with mental illness, and those using stimulants receive care.

The clinical trials for long-acting injectable antiretrovirals included only people who were virologically suppressed, which is also the Food and Drug Administration criteria for use. However, this clinic offered long-acting injections to patients with viremia because it was too difficult for them to take a daily pill.

In a comment, Dr. Gandhi, director of the University of California, San Francisco’s Center for AIDS Research, said: “We don’t call people hard to reach, we call them hardly reached because it’s not their fault.” There are just all of these issues that have made it harder for them to take medication consistently.

Dr. Gandhi reported that, of the 133 people being treated with long-acting injectable cabotegravir and rilpivirine at the clinic through this program, 57 had viremia at baseline.

However, only two of these patients experienced virologic failure while on the injectable antiretroviral program. The overall virologic failure rate was 1.5%, which was equivalent to that seen in clinical trials in virologically suppressed individuals.

The results presented at the conference and were also published in Annals of Internal Medicine.

The clinic found that 73% of people attended their injection appointments on time, and those who did not were followed up with telephone calls to ensure they received their injection within the 14-day window.

Dr. Gandhi said people were highly motivated to turn up for their injection appointments. “They are virologically suppressed, so it feels so amazing. They’re self-motivated for the first time to want to get an injection.”

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

*Correction, 8/4/23: An earlier version of this article misstated Dr. Patel's university affiliation.

TOPLINE:

Researchers detected single-nucleotide polymorphisms (SNPs) tied to osteoporosis risk from a drop of blood, in a 15-minute, inexpensive test using an investigational electrochemical device.

METHODOLOGY:

• 10-mcL finger-prick blood samples from 15 people were diluted 1:5 and subjected to rapid thermolysis (30 seconds at 95° C) to extract the DNA.
• Blood samples with the lysed DNA, and negative controls, were applied to an investigational, generic, portable electrochemical device (Labman Automation), in which individual gold electrodes were covered with reverse primers for each of five osteoporosis-associated SNPs.
• DNA in the blood samples that matched the SNPs bound to these electrodes, and the reaction was amplified with recombinase polymerase labeled with ferrocene, which facilitates electrochemical detection.
• Five SNPs associated with an increased risk of developing osteoporosis and risk for fracture were detected in the 15 blood samples, and the results were validated using TaqMan SNP genotyping assays and Sanger sequencing.

TAKEAWAYS:

• Measuring bone mineral density by dual-energy x-ray absorptiometry reliably predicts fracture risk, but only when a significant amount of bone is already lost.
• Researchers developed and validated a generic, battery-operable, portable device to detect osteoporosis-associated SNPs from a finger-prick blood sample, with no need for DNA extraction or purification.
• The entire assay from the addition of the thermolyzed blood sample to the readout of the results was complete in just 15 minutes, with a cost per SNP, on a laboratory scale, including the cost of the electrode array and all reagents, of 0.3 euro (0.33 USD).
• The researchers previously showed that the device identified an SNP associated with rifampicin resistance in Mycobacterium tuberculosis in a sputum sample, and an SNP linked with cardiomyopathy in blood; they plan to test a scaled-up version of the device.

IN PRACTICE:

“The platform is completely generic and has immense potential for deployment at the point of need in an automated device for targeted SNP genotyping with the only required end-user intervention being sample addition,” said the authors in their report.

STUDY DETAILS:

The authors, from INTERFIBIO Research Group, Tarragona, Spain, as well as Austria, the Czech Republic, and the Netherlands, published their findings in ACS Central Science.

LIMITATIONS:

The researchers did not report any study limitations.

DISCLOSURES:

The study received no commercial funding. The authors reported no relevant financial relationships.

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

TOPLINE:

Researchers detected single-nucleotide polymorphisms (SNPs) tied to osteoporosis risk from a drop of blood, in a 15-minute, inexpensive test using an investigational electrochemical device.

METHODOLOGY:

• 10-mcL finger-prick blood samples from 15 people were diluted 1:5 and subjected to rapid thermolysis (30 seconds at 95° C) to extract the DNA.
• Blood samples with the lysed DNA, and negative controls, were applied to an investigational, generic, portable electrochemical device (Labman Automation), in which individual gold electrodes were covered with reverse primers for each of five osteoporosis-associated SNPs.
• DNA in the blood samples that matched the SNPs bound to these electrodes, and the reaction was amplified with recombinase polymerase labeled with ferrocene, which facilitates electrochemical detection.
• Five SNPs associated with an increased risk of developing osteoporosis and risk for fracture were detected in the 15 blood samples, and the results were validated using TaqMan SNP genotyping assays and Sanger sequencing.

TAKEAWAYS:

• Measuring bone mineral density by dual-energy x-ray absorptiometry reliably predicts fracture risk, but only when a significant amount of bone is already lost.
• Researchers developed and validated a generic, battery-operable, portable device to detect osteoporosis-associated SNPs from a finger-prick blood sample, with no need for DNA extraction or purification.
• The entire assay from the addition of the thermolyzed blood sample to the readout of the results was complete in just 15 minutes, with a cost per SNP, on a laboratory scale, including the cost of the electrode array and all reagents, of 0.3 euro (0.33 USD).
• The researchers previously showed that the device identified an SNP associated with rifampicin resistance in Mycobacterium tuberculosis in a sputum sample, and an SNP linked with cardiomyopathy in blood; they plan to test a scaled-up version of the device.

IN PRACTICE:

“The platform is completely generic and has immense potential for deployment at the point of need in an automated device for targeted SNP genotyping with the only required end-user intervention being sample addition,” said the authors in their report.

STUDY DETAILS:

The authors, from INTERFIBIO Research Group, Tarragona, Spain, as well as Austria, the Czech Republic, and the Netherlands, published their findings in ACS Central Science.

LIMITATIONS:

The researchers did not report any study limitations.

DISCLOSURES:

The study received no commercial funding. The authors reported no relevant financial relationships.

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

TOPLINE:

Researchers detected single-nucleotide polymorphisms (SNPs) tied to osteoporosis risk from a drop of blood, in a 15-minute, inexpensive test using an investigational electrochemical device.

METHODOLOGY:

• 10-mcL finger-prick blood samples from 15 people were diluted 1:5 and subjected to rapid thermolysis (30 seconds at 95° C) to extract the DNA.
• Blood samples with the lysed DNA, and negative controls, were applied to an investigational, generic, portable electrochemical device (Labman Automation), in which individual gold electrodes were covered with reverse primers for each of five osteoporosis-associated SNPs.
• DNA in the blood samples that matched the SNPs bound to these electrodes, and the reaction was amplified with recombinase polymerase labeled with ferrocene, which facilitates electrochemical detection.
• Five SNPs associated with an increased risk of developing osteoporosis and risk for fracture were detected in the 15 blood samples, and the results were validated using TaqMan SNP genotyping assays and Sanger sequencing.

TAKEAWAYS:

• Measuring bone mineral density by dual-energy x-ray absorptiometry reliably predicts fracture risk, but only when a significant amount of bone is already lost.
• Researchers developed and validated a generic, battery-operable, portable device to detect osteoporosis-associated SNPs from a finger-prick blood sample, with no need for DNA extraction or purification.
• The entire assay from the addition of the thermolyzed blood sample to the readout of the results was complete in just 15 minutes, with a cost per SNP, on a laboratory scale, including the cost of the electrode array and all reagents, of 0.3 euro (0.33 USD).
• The researchers previously showed that the device identified an SNP associated with rifampicin resistance in Mycobacterium tuberculosis in a sputum sample, and an SNP linked with cardiomyopathy in blood; they plan to test a scaled-up version of the device.

IN PRACTICE:

“The platform is completely generic and has immense potential for deployment at the point of need in an automated device for targeted SNP genotyping with the only required end-user intervention being sample addition,” said the authors in their report.

STUDY DETAILS:

The authors, from INTERFIBIO Research Group, Tarragona, Spain, as well as Austria, the Czech Republic, and the Netherlands, published their findings in ACS Central Science.

LIMITATIONS:

The researchers did not report any study limitations.

DISCLOSURES:

The study received no commercial funding. The authors reported no relevant financial relationships.

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

At the new Walnut Creek Clinic in the East Bay of the San Francisco Bay area, kids get a “Comfort Promise.”

The clinic extends the work of the Stad Center for Pediatric Pain, Palliative & Integrative Medicine beyond the locations in University of California San Francisco Benioff Children’s Hospitals in San Francisco and Oakland.

At Walnut Creek, clinical acupuncturists, massage therapists, and specialists in hypnosis complement advanced medical care with integrative techniques.

The “Comfort Promise” program, which is being rolled out at that clinic and other UCSF pediatric clinics through the end of 2024, is the clinicians’ pledge to do everything in their power to make tests, infusions, and vaccinations “practically pain free.”

Needle sticks, for example, can be a common source of pain and anxiety for kids. Techniques to minimize pain vary by age. Among the ways the clinicians minimize needle pain for a child 6- to 12-years-old are:

• Giving the child control options to pick which arm; and watch the injection, pause it, or stop it with a communication sign.
• Introducing memory shaping by asking the child about the experience afterward and presenting it in a positive way by praising the acts of sitting still, breathing deeply, or being brave.
• Using distractors such as asking the child to hold a favorite item from home, storytelling, coloring, singing, or using breathing exercises.

Stefan Friedrichsdorf, MD, chief of the UCSF division of pediatric pain, palliative & integrative medicine, said in a statement: “For kids with chronic pain, complex pain medications can cause more harm than benefit. Our goal is to combine exercise and physical therapy with integrative medicine and skills-based psychotherapy to help them become pain free in their everyday life.”
 

Bundling appointments for early impact

At Lurie Children’s Hospital of Chicago, the chronic pain treatment program bundles visits with experts in several disciplines, include social workers, psychologists, and physical therapists, in addition to the medical team, so that patients can complete a first round of visits with multiple specialists in a short period, as opposed to several months.

Natalie Weatherred, APRN-NP, CPNP-PC, a pediatric nurse practitioner in anesthesiology and the pain clinic coordinator, said in an interview that the up-front visits involve between four and eight follow-up sessions in a short period with everybody in the multidisciplinary team “to really help jump-start their pain treatment.”

She pointed out that many families come from distant parts of the state or beyond so the bundled appointments are also important for easing burden on families.

Sarah Duggan, APRN-NP, CPNP-PC, also a pediatric nurse practitioner in anesthesiology at Lurie’s, pointed out that patients at their clinic often have other chronic conditions as well, such as such as postural orthostatic tachycardia syndrome so the care integration is particularly important.

“We can get them the appropriate care that they need and the resources they need, much sooner than we would have been able to do 5 or 10 years ago,” Ms. Duggan said.
 

Virtual reality distraction instead of sedation

Henry Huang, MD, anesthesiologist and pain physician at Texas Children’s Hospital, Houston, said a special team there collaborates with the Chariot Program at Stanford (Calif.) University and incorporates virtual reality to distract children from pain and anxiety and harness their imaginations during induction for anesthesia, intravenous placement, and vaccinations.

“At our institution we’ve been recruiting patients to do a proof of concept to do virtual reality distraction for pain procedures, such as nerve blocks or steroid injections,” Dr. Huang said.

Traditionally, kids would have received oral or intravenous sedation to help them cope with the fear and pain.

“We’ve been successful in several cases without relying on any sedation,” he said. “The next target is to expand that to the chronic pain population.”

The distraction techniques are promising for a wide range of ages, he said, and the programming is tailored to the child’s ability to interact with the technology.

He said he is also part of a group promoting use of ultrasound instead of x-rays to guide injections to the spine and chest to reduce children’s exposure to radiation. His group is helping teach these methods to other clinicians nationally.

Dr. Huang said the most important development in chronic pediatric pain has been the growth of rehab centers that include the medical team, and practitioners from psychology as well as occupational and physical therapy.

“More and more hospitals are recognizing the importance of these pain rehab centers,” he said.

The problem, Dr. Huang said, is that these programs have always been resource intensive and involve highly specialized clinicians. The cost and the limited number of specialists make it difficult for widespread rollout.

“That’s always been the challenge from the pediatric pain world,” he said.
 

Recognizing the complexity of kids’ chronic pain

Angela Garcia, MD, a consulting physician for pediatric rehabilitation medicine at UPMC Children’s Hospital of Pittsburgh said recognizing the validity and complexity of pediatric pain has led to multidisciplinary approaches and specialty clinics for chronic pain instead of primarily pharmaceutical solutions.

Techniques such as biofeedback and acupuncture are becoming more mainstream in pediatric chronic care, she said.

At the UPMC clinic, children and their families talk with a care team about their values and what they want to accomplish in managing the child’s pain. They ask what the pain is preventing the child from doing.

“Their goals really are our goals,” she said.

She said she also refers almost all patients to one of the center’s pain psychologists.

“Pain is biopsychosocial,” she said. “We want to make sure we’re addressing how to cope with pain.”

Dr. Garcia said she hopes nutritional therapy is one of the next approaches the clinic will incorporate, particularly surrounding how dietary changes can reduce inflammation “and heal the body from the inside out.”

She said the hospital is also looking at developing an inpatient pain program for kids whose functioning has changed so drastically that they need more intensive therapies.

Whatever the treatment approach, she said, addressing the pain early is critical.

“There is an increased risk of a child with chronic pain becoming an adult with chronic pain,” Dr. Garcia pointed out, “and that can lead to a decrease in the ability to participate in society.”

Ms. Weatherred, Ms. Duggan, Dr. Huang, and Dr. Garcia reported no relevant financial relationships.

At the new Walnut Creek Clinic in the East Bay of the San Francisco Bay area, kids get a “Comfort Promise.”

The clinic extends the work of the Stad Center for Pediatric Pain, Palliative & Integrative Medicine beyond the locations in University of California San Francisco Benioff Children’s Hospitals in San Francisco and Oakland.

At Walnut Creek, clinical acupuncturists, massage therapists, and specialists in hypnosis complement advanced medical care with integrative techniques.

The “Comfort Promise” program, which is being rolled out at that clinic and other UCSF pediatric clinics through the end of 2024, is the clinicians’ pledge to do everything in their power to make tests, infusions, and vaccinations “practically pain free.”

Needle sticks, for example, can be a common source of pain and anxiety for kids. Techniques to minimize pain vary by age. Among the ways the clinicians minimize needle pain for a child 6- to 12-years-old are:

• Giving the child control options to pick which arm; and watch the injection, pause it, or stop it with a communication sign.
• Introducing memory shaping by asking the child about the experience afterward and presenting it in a positive way by praising the acts of sitting still, breathing deeply, or being brave.
• Using distractors such as asking the child to hold a favorite item from home, storytelling, coloring, singing, or using breathing exercises.

Stefan Friedrichsdorf, MD, chief of the UCSF division of pediatric pain, palliative & integrative medicine, said in a statement: “For kids with chronic pain, complex pain medications can cause more harm than benefit. Our goal is to combine exercise and physical therapy with integrative medicine and skills-based psychotherapy to help them become pain free in their everyday life.”
 

Bundling appointments for early impact

At Lurie Children’s Hospital of Chicago, the chronic pain treatment program bundles visits with experts in several disciplines, include social workers, psychologists, and physical therapists, in addition to the medical team, so that patients can complete a first round of visits with multiple specialists in a short period, as opposed to several months.

Natalie Weatherred, APRN-NP, CPNP-PC, a pediatric nurse practitioner in anesthesiology and the pain clinic coordinator, said in an interview that the up-front visits involve between four and eight follow-up sessions in a short period with everybody in the multidisciplinary team “to really help jump-start their pain treatment.”

She pointed out that many families come from distant parts of the state or beyond so the bundled appointments are also important for easing burden on families.

Sarah Duggan, APRN-NP, CPNP-PC, also a pediatric nurse practitioner in anesthesiology at Lurie’s, pointed out that patients at their clinic often have other chronic conditions as well, such as such as postural orthostatic tachycardia syndrome so the care integration is particularly important.

“We can get them the appropriate care that they need and the resources they need, much sooner than we would have been able to do 5 or 10 years ago,” Ms. Duggan said.
 

Virtual reality distraction instead of sedation

Henry Huang, MD, anesthesiologist and pain physician at Texas Children’s Hospital, Houston, said a special team there collaborates with the Chariot Program at Stanford (Calif.) University and incorporates virtual reality to distract children from pain and anxiety and harness their imaginations during induction for anesthesia, intravenous placement, and vaccinations.

“At our institution we’ve been recruiting patients to do a proof of concept to do virtual reality distraction for pain procedures, such as nerve blocks or steroid injections,” Dr. Huang said.

Traditionally, kids would have received oral or intravenous sedation to help them cope with the fear and pain.

“We’ve been successful in several cases without relying on any sedation,” he said. “The next target is to expand that to the chronic pain population.”

The distraction techniques are promising for a wide range of ages, he said, and the programming is tailored to the child’s ability to interact with the technology.

He said he is also part of a group promoting use of ultrasound instead of x-rays to guide injections to the spine and chest to reduce children’s exposure to radiation. His group is helping teach these methods to other clinicians nationally.

Dr. Huang said the most important development in chronic pediatric pain has been the growth of rehab centers that include the medical team, and practitioners from psychology as well as occupational and physical therapy.

“More and more hospitals are recognizing the importance of these pain rehab centers,” he said.

The problem, Dr. Huang said, is that these programs have always been resource intensive and involve highly specialized clinicians. The cost and the limited number of specialists make it difficult for widespread rollout.

“That’s always been the challenge from the pediatric pain world,” he said.
 

Recognizing the complexity of kids’ chronic pain

Angela Garcia, MD, a consulting physician for pediatric rehabilitation medicine at UPMC Children’s Hospital of Pittsburgh said recognizing the validity and complexity of pediatric pain has led to multidisciplinary approaches and specialty clinics for chronic pain instead of primarily pharmaceutical solutions.

Techniques such as biofeedback and acupuncture are becoming more mainstream in pediatric chronic care, she said.

At the UPMC clinic, children and their families talk with a care team about their values and what they want to accomplish in managing the child’s pain. They ask what the pain is preventing the child from doing.

“Their goals really are our goals,” she said.

She said she also refers almost all patients to one of the center’s pain psychologists.

“Pain is biopsychosocial,” she said. “We want to make sure we’re addressing how to cope with pain.”

Dr. Garcia said she hopes nutritional therapy is one of the next approaches the clinic will incorporate, particularly surrounding how dietary changes can reduce inflammation “and heal the body from the inside out.”

She said the hospital is also looking at developing an inpatient pain program for kids whose functioning has changed so drastically that they need more intensive therapies.

Whatever the treatment approach, she said, addressing the pain early is critical.

“There is an increased risk of a child with chronic pain becoming an adult with chronic pain,” Dr. Garcia pointed out, “and that can lead to a decrease in the ability to participate in society.”

Ms. Weatherred, Ms. Duggan, Dr. Huang, and Dr. Garcia reported no relevant financial relationships.

At the new Walnut Creek Clinic in the East Bay of the San Francisco Bay area, kids get a “Comfort Promise.”

The clinic extends the work of the Stad Center for Pediatric Pain, Palliative & Integrative Medicine beyond the locations in University of California San Francisco Benioff Children’s Hospitals in San Francisco and Oakland.

At Walnut Creek, clinical acupuncturists, massage therapists, and specialists in hypnosis complement advanced medical care with integrative techniques.

The “Comfort Promise” program, which is being rolled out at that clinic and other UCSF pediatric clinics through the end of 2024, is the clinicians’ pledge to do everything in their power to make tests, infusions, and vaccinations “practically pain free.”

Needle sticks, for example, can be a common source of pain and anxiety for kids. Techniques to minimize pain vary by age. Among the ways the clinicians minimize needle pain for a child 6- to 12-years-old are:

• Giving the child control options to pick which arm; and watch the injection, pause it, or stop it with a communication sign.
• Introducing memory shaping by asking the child about the experience afterward and presenting it in a positive way by praising the acts of sitting still, breathing deeply, or being brave.
• Using distractors such as asking the child to hold a favorite item from home, storytelling, coloring, singing, or using breathing exercises.

Stefan Friedrichsdorf, MD, chief of the UCSF division of pediatric pain, palliative & integrative medicine, said in a statement: “For kids with chronic pain, complex pain medications can cause more harm than benefit. Our goal is to combine exercise and physical therapy with integrative medicine and skills-based psychotherapy to help them become pain free in their everyday life.”
 

Bundling appointments for early impact

At Lurie Children’s Hospital of Chicago, the chronic pain treatment program bundles visits with experts in several disciplines, include social workers, psychologists, and physical therapists, in addition to the medical team, so that patients can complete a first round of visits with multiple specialists in a short period, as opposed to several months.

Natalie Weatherred, APRN-NP, CPNP-PC, a pediatric nurse practitioner in anesthesiology and the pain clinic coordinator, said in an interview that the up-front visits involve between four and eight follow-up sessions in a short period with everybody in the multidisciplinary team “to really help jump-start their pain treatment.”

She pointed out that many families come from distant parts of the state or beyond so the bundled appointments are also important for easing burden on families.

Sarah Duggan, APRN-NP, CPNP-PC, also a pediatric nurse practitioner in anesthesiology at Lurie’s, pointed out that patients at their clinic often have other chronic conditions as well, such as such as postural orthostatic tachycardia syndrome so the care integration is particularly important.

“We can get them the appropriate care that they need and the resources they need, much sooner than we would have been able to do 5 or 10 years ago,” Ms. Duggan said.
 

Virtual reality distraction instead of sedation

Henry Huang, MD, anesthesiologist and pain physician at Texas Children’s Hospital, Houston, said a special team there collaborates with the Chariot Program at Stanford (Calif.) University and incorporates virtual reality to distract children from pain and anxiety and harness their imaginations during induction for anesthesia, intravenous placement, and vaccinations.

“At our institution we’ve been recruiting patients to do a proof of concept to do virtual reality distraction for pain procedures, such as nerve blocks or steroid injections,” Dr. Huang said.

Traditionally, kids would have received oral or intravenous sedation to help them cope with the fear and pain.

“We’ve been successful in several cases without relying on any sedation,” he said. “The next target is to expand that to the chronic pain population.”

The distraction techniques are promising for a wide range of ages, he said, and the programming is tailored to the child’s ability to interact with the technology.

He said he is also part of a group promoting use of ultrasound instead of x-rays to guide injections to the spine and chest to reduce children’s exposure to radiation. His group is helping teach these methods to other clinicians nationally.

Dr. Huang said the most important development in chronic pediatric pain has been the growth of rehab centers that include the medical team, and practitioners from psychology as well as occupational and physical therapy.

“More and more hospitals are recognizing the importance of these pain rehab centers,” he said.

The problem, Dr. Huang said, is that these programs have always been resource intensive and involve highly specialized clinicians. The cost and the limited number of specialists make it difficult for widespread rollout.

“That’s always been the challenge from the pediatric pain world,” he said.
 

Recognizing the complexity of kids’ chronic pain

Angela Garcia, MD, a consulting physician for pediatric rehabilitation medicine at UPMC Children’s Hospital of Pittsburgh said recognizing the validity and complexity of pediatric pain has led to multidisciplinary approaches and specialty clinics for chronic pain instead of primarily pharmaceutical solutions.

Techniques such as biofeedback and acupuncture are becoming more mainstream in pediatric chronic care, she said.

At the UPMC clinic, children and their families talk with a care team about their values and what they want to accomplish in managing the child’s pain. They ask what the pain is preventing the child from doing.

“Their goals really are our goals,” she said.

She said she also refers almost all patients to one of the center’s pain psychologists.

“Pain is biopsychosocial,” she said. “We want to make sure we’re addressing how to cope with pain.”

Dr. Garcia said she hopes nutritional therapy is one of the next approaches the clinic will incorporate, particularly surrounding how dietary changes can reduce inflammation “and heal the body from the inside out.”

She said the hospital is also looking at developing an inpatient pain program for kids whose functioning has changed so drastically that they need more intensive therapies.

Whatever the treatment approach, she said, addressing the pain early is critical.

“There is an increased risk of a child with chronic pain becoming an adult with chronic pain,” Dr. Garcia pointed out, “and that can lead to a decrease in the ability to participate in society.”

Ms. Weatherred, Ms. Duggan, Dr. Huang, and Dr. Garcia reported no relevant financial relationships.

Off-label prescribing (OLP) refers to the practice of using medications for indications outside of those approved by the FDA, or in dosages, dose forms, or patient populations that have not been approved by the FDA.¹ OLP is common, occurring in many practice settings and nearly every medical specialty. In a 2006 review, Radley et al² found OLP accounted for 21% of the overall use of 160 common medications. The frequency of OLP varies between medication classes. Off-label use of anticonvulsants, antidepressants, and antipsychotics tends to be higher than that of other medications.^3,4 OLP is often more common in patient populations unlikely to be included in clinical trials due to ethical or logistical difficulties, such as pediatric patients and individuals who are pregnant. The Box summarizes several components that contribute to the prevalence of OLP and explains why this practice is often necessary for treating certain substance-related and addictive disorders.

Box

Several important medicolegal and ethical considerations surround OLP. The FDA prohibits off-label promotion, in which manufacturers advertise the use of a medication for off-label use.⁵ However, regulations allow physicians to use their best clinical judgment when prescribing medications for off-label use. When considering off-label use of any medication, physicians should review the most up-to-date research, including clinical trials, case reports, and reviews to safely support their decision-making. OLP should be guided by ethical principles such as autonomy, beneficence, nonmaleficence, and justice. Physicians should obtain informed consent by conducting an appropriate discussion of the risks, benefits, and alternatives of off-label medications. This conversation should be clearly documented, and physicians should provide written material regarding off-label options to patients when available. Finally, physicians should verify their patients’ understanding of this discussion, and allow patients to accept or decline off-label medications without pressure.

This article focuses on current and potential future medications available for OLP to treat patients with alcohol use disorder (AUD), gambling disorder (GD), stimulant use disorder, and cannabis use disorder.

Alcohol use disorder

CASE 1

Ms. X, age 67, has a history of severe AUD, mild renal impairment, and migraines. She presents to the outpatient clinic seeking help to drink less alcohol. Ms. X reports drinking 1 to 2 bottles of wine each day. She was previously treated for AUD but was not helped by naltrexone and did not tolerate disulfiram (abstinence was not her goal and she experienced significant adverse effects). Ms. X says she has a medical history of chronic migraines but denies other medical issues. The treatment team discusses alternative pharmacologic options, including acamprosate and topiramate. After outlining the dosing schedule and risks/benefits with Ms. X, you make the joint decision to start topiramate to reduce alcohol cravings and target her migraine symptoms.

Only 3 medications are FDA-approved for treating AUD: disulfiram, naltrexone (oral and injectable formulations), and acamprosate. Off-label options for AUD treatment include gabapentin, topiramate, and baclofen.

Gabapentin is FDA-approved for treating postherpetic neuralgia and partial seizures in patients age ≥3. The exact mechanism of action is unclear, though its effects are possibly related to its activity as a calcium channel ligand. It also carries a structural resemblance to gamma-aminobutyric acid (GABA), though it lacks activity at GABA receptors.

Several randomized controlled trials (RCTs) evaluating the efficacy of gabapentin for AUD produced promising results. In a comparison of gabapentin vs placebo for AUD, Anton et al⁶ found gabapentin led to significant increases in the number of participants with total alcohol abstinence and participants who reported reduced drinking. Notably, the effect was most prominent in those with heavy drinking patterns and pretreatment alcohol withdrawal symptoms. A total of 41% of participants with high alcohol withdrawal scores on pretreatment evaluation achieved total abstinence while taking gabapentin, compared to 1% in the placebo group.⁶ A meta-analysis of gabapentin for AUD by Kranzler et al⁷ included 7 RCTs and 32 effect measures. It found that although all outcome measures favored gabapentin over placebo, only the percentage of heavy drinking days was significantly different.

Gabapentin is dosed between 300 to 600 mg 3 times per day, but 1 study found that a higher dose (1,800 mg/d) was associated with better outcomes.⁸ Common adverse effects include sedation, dizziness, peripheral edema, and ataxia.

Continue to: Topiramate

Topiramate blocks voltage-gated sodium channels and enhances GABA-A receptor activity.⁹ It is indicated for the treatment of seizures, migraine prophylaxis, weight management, and weight loss. Several clinical trials, including RCTs,^10-12 demonstrated that topiramate was superior to placebo in reducing the percentage of heavy drinking days and overall drinking days. Some also showed that topiramate was associated with abstinence and reduced craving levels.^12,13 A meta-analysis by Blodgett et al¹⁴ found that compared to placebo, topiramate lowered the rate of heavy drinking and increased abstinence.

Topiramate is dosed from 50 to 150 mg twice daily, although some studies suggest a lower dose (≤75 mg/d) may be associated with clinical benefits.^15,16 One important clinical consideration: topiramate must follow a slow titration schedule (4 to 6 weeks) to increase tolerability and avoid adverse effects. Common adverse effects include sedation, word-finding difficulty, paresthesia, increased risk for renal calculi, dizziness, anorexia, and alterations in taste.

Baclofen is a GABA-B agonist FDA-approved for the treatment of muscle spasticity related to multiple sclerosis and reversible spasticity related to spinal cord lesions and multiple sclerosis. Of note, it is approved for treatment of AUD in Europe.

In a meta-analysis of 13 RCTs, Pierce et al¹⁷ found a greater likelihood of abstinence and greater time to first lapse of drinking with baclofen compared to placebo. Interestingly, a subgroup analysis found that the positive effects were limited to trials that used 30 to 60 mg/d of baclofen, and not evident in those that used higher doses. Additionally, there was no difference between baclofen and placebo with regard to several important outcomes, including alcohol cravings, anxiety, depression, or number of total abstinent days. A review by Andrade¹⁸ proposed that individualized treatment with high-dose baclofen (30 to 300 mg/d) may be a useful second-line approach in heavy drinkers who wish to reduce their alcohol intake.

Continue to: Before starting baclofen...

Before starting baclofen, patients should be informed about its adverse effects. Common adverse effects include sedation and motor impairment. More serious but less common adverse effects include seizures, respiratory depression with sleep apnea, severe mood disorders (ie, mania, depression, or suicide risk), and mental confusion. Baclofen should be gradually discontinued, because there is some risk of clinical withdrawal symptoms (ie, agitation, confusion, seizures, or delirium).

Among the medications discussed in this section, the evidence for gabapentin and topiramate is moderate to strong, while the evidence for baclofen is overall weaker or mixed. The American Psychiatric Association’s Practice Guideline suggests offering gabapentin or topiramate to patients with moderate to severe AUD whose goal is to achieve abstinence or reduce alcohol use, or those who prefer gabapentin or topiramate or cannot tolerate or have not responded to naltrexone and acamprosate.¹⁹ Clinicians must ensure patients have no contra­indications to the use of these medications. Due to the moderate quality evidence for a significant reduction in heavy drinking and increased abstinence,^14,20 a practice guideline from the US Department of Veterans Affairs and US Department of Defense²¹ recommends topiramate as 1 of 2 first-line treatments (the other is naltrexone). This guideline suggests gabapentin as a second-line treatment for AUD.²¹

Gambling disorder

CASE 2

Mr. P, age 28, seeks treatment for GD and cocaine use disorder. He reports a 7-year history of sports betting that has increasingly impaired his functioning over the past year. He lost his job, savings, and familial relationships due to his impulsive and risky behavior. Mr. P also reports frequent cocaine use, about 2 to 3 days per week, mostly on the weekends. The psychiatrist tells Mr. P there is no FDA-approved pharmacologic treatment for GD or cocaine use disorder. The psychiatrist discusses the option of naltrexone as off-label treatment for GD with the goal of reducing Mr. P’s urges to gamble, and points to possible benefits for cocaine use disorder.

GD impacts approximately 0.5% of the adult US population and is often co-occurring with substance use disorders.²² It is thought to share neurobiological and clinical similarities with substance use disorders.²³ There are currently no FDA-approved medications to treat the disorder. In studies of GD, treatment success with antidepressants and mood stabilizers has not been consistent,^23,24 but some promising results have been published for the opioid receptor antagonist naltrexone^24-29and N-acetylcysteine (NAC).^30-32

Naltrexone is thought to reduce gambling behavior and urges via downstream modulation of mesolimbic dopamine circuitry.²⁴ It is FDA-approved for the treatment of AUD and opioid use disorder. Open-label RCTs have found a reduction in gambling urges and behavior with daily naltrexone.^25-27 Dosing at 50 mg/d appears to be just as efficacious as higher doses such as 100 and 150 mg/d.²⁷ When used as a daily as-needed medication for strong gambling urges or if an individual was planning to gamble, naltrexone 50 mg/d was not effective.²⁸

Continue to: Naltrexone typically is started...

Naltrexone typically is started at 25 mg/d to assess tolerability and quickly titrated to 50 mg/d. When titrating, common adverse effects include nausea, vomiting, and transient elevations in transaminases. Another opioid antagonist, nalmefene, has also been studied in patients with GD. An RCT by Grant et al²⁹ that evaluated 207 patients found that compared with placebo, nalmefene 25 mg/d for 16 weeks was associated with a significant reduction in gambling assessment scores. In Europe, nalmefene is approved for treating AUD but the oral formulation is not currently available in the US.

N-acetylcysteine is thought to potentially reverse neuronal dysfunction seen in addictive disorders by glutamatergic modulation.³⁰ Research investigating NAC for GD is scarce. A pilot study found 16 of 27 patients with GD reduced gambling behavior with a mean dose of 1,476.9 mg/d.³¹ An additional study investigating the addition of NAC to behavioral therapy in nicotine-dependent individuals with pathologic gambling found a reduction in problem gambling after 18 weeks (6 weeks + 3 months follow-up).³² Common but mild adverse effects associated with NAC are nausea, vomiting, and diarrhea.

A meta-analysis by Goslar et al³³ that reviewed 34 studies (1,340 participants) found pharmacologic treatments were associated with large and medium pre-post reductions in global severity, frequency, and financial loss in patients with GD. RCTs studying opioid antagonists and mood stabilizers (combined with a cognitive intervention) as well as lithium for patients with comorbid bipolar disorder and GD demonstrated promising results.³³

Stimulant use disorder

There are no FDA-approved medications for stimulant use disorder. Multiple off-label options have been studied for the treatment of methamphetamine abuse and cocaine abuse.

Methamphetamine use has been expanding over the past decade with a 3.6-fold increase in positive methamphetamine screens in overdose deaths from 2011 to 2016.³⁴ Pharmacologic options studied for OLP of methamphetamine use disorder include mirtazapine, bupropion, naltrexone, and topiramate.

Continue to: Mirtazapine

Mirtazapine is an atypical antidepressant whose mechanism of action includes modulation of the serotonin, norepinephrine, and alpha-2 adrenergic systems. It is FDA-approved for the treatment of major depressive disorder (MDD). In a randomized placebo-controlled study, mirtazapine 30 mg/d at night was found to decrease methamphetamine use for active users and led to decreased sexual risk in men who have sex with men.³⁵ These results were supported by an additional RCT in which mirtazapine 30 mg/d significantly reduced rates of methamphetamine use vs placebo at 24 and 36 weeks despite poor medication adherence.³⁶ Adverse effects to monitor in patients treated with mirtazapine include increased appetite, weight gain, sedation, and constipation.

Bupropion is a norepinephrine dopamine reuptake inhibitor that produces increased neurotransmission of norepinephrine and dopamine in the CNS. It is FDA-approved for the treatment of MDD and as an aid for smoking cessation. Bupropion has been studied for methamphetamine use disorder with mixed results. In a randomized placebo-controlled trial, bupropion sustained release 150 mg twice daily was not more effective than placebo in reducing methamphetamine use.³⁷ However, the extended-release formulation of bupropion 450 mg/d combined with long-acting injectable naltrexone was associated with a reduction in methamphetamine use over 12 weeks.³⁸ Bupropion is generally well tolerated; common adverse effects include insomnia, tremor, headache, and dizziness.

Naltrexone. Data about using oral naltrexone to treat stimulant use disorders are limited. A randomized, placebo-controlled trial by Jayaram-Lindström et al³⁹ found naltrexone 50 mg/d significantly reduced amphetamine use compared to placebo. Additionally, naltrexone 50 and 150 mg/d have been shown to reduce cocaine use over time in combination with therapy for cocaine-dependent patients and those dependent on alcohol and cocaine.^40,41

Topiramate has been studied for the treatment of cocaine use disorder. It is hypothesized that modulation of the mesocorticolimbic dopamine system may contribute to decreased cocaine cravings.⁴² A pilot study by Kampman et al⁴³ found that after an 8-week titration of topiramate to 200 mg/d, individuals were more likely to achieve cocaine abstinence compared to those who receive placebo. In an RCT, Elkashef et al⁴⁴ did not find topiramate assisted with increased abstinence of methamphetamine in active users at a target dose of 200 mg/d. However, it was associated with reduced relapse rates in individuals who were abstinent prior to the study.⁴⁴ At a target dose of 300 mg/d, topiramate also outperformed placebo in decreasing days of cocaine use.⁴² Adverse effects of topiramate included paresthesia, alteration in taste, and difficulty with concentration.

Cannabis use disorder

In recent years, cannabis use in the US has greatly increased⁴⁵ but no medications are FDA-approved for treating cannabis use disorder. Studies of pharmacologic options for cannabis use disorder have had mixed results.⁴⁶ A meta-analysis by Bahji et al⁴⁷ of 24 studies investigating pharmacotherapies for cannabis use disorder highlighted the lack of adequate evidence. In this section, we focus on a few positive trials of NAC and gabapentin.

Continue to: N-acetylcysteine

N-acetylcysteine. Studies investigating NAC 1,200 mg twice daily have been promising in adolescent and adult populations.^48-50 There are some mixed results, however. A large RCT found NAC 1,200 mg twice daily was not better than placebo in helping adults achieve abstinence from cannabis.⁵¹

Gabapentin may be a viable option for treating cannabis use disorder. A pilot study by Mason et al⁵² found gabapentin 1,200 mg/d was more effective than placebo at reducing cannabis use among treatment-seeking adults.

When and how to consider OLP

OLP for addictive disorders is common and often necessary. This is primarily due to limitations of the FDA-approved medications and because there are no FDA-approved medications for many substance-related and addictive disorders (ie, GD, cannabis use disorder, and stimulant use disorder). When assessing pharmacotherapy options, if FDA-approved medications are available for certain diagnoses, clinicians should first consider them. The off-label medications discussed in this article are outlined in the Table.^{6-21,24-28,30-33,35-44,48-52}

The overall level of evidence to support the use of off-label medications is lower than that of FDA-approved medications, which contributes to potential medicolegal concerns of OLP. Off-label medications should be considered when there are no FDA-approved medications available, and the decision to use off-label medications should be based on evidence from the literature and current standard of care. Additionally, OLP is necessary if a patient cannot tolerate FDA-approved medications, is not helped by FDA-approved treatments, or when there are other clinical reasons to choose a particular off-label medication. For example, if a patient has comorbid AUD and obesity (or migraines), using topiramate may be appropriate because it may target alcohol cravings and can be helpful for weight loss (and migraine prophylaxis). Similarly, for patients with AUD and neuropathic pain, using gabapentin can be considered for its dual therapeutic effects.

It is critical for clinicians to understand the landscape of off-label options for treating addictive disorders. Additional research in the form of RCTs is needed to better clarify the efficacy and adverse effects of these treatments.

Continue to: Bottom Line

Off-label prescribing is prevalent in practice, including in the treatment of substance-related and addictive disorders. When considering off-label use of any medication, clinicians should review the most recent research, obtain informed consent from patients, and verify patients’ understanding of the potential risks and adverse effects associated with the particular medication.

Related Resources

• Joshi KG, Frierson RL. Off-label prescribing: how to limit your liability. Current Psychiatry. 2020;19(9):12,39. doi:10.12788/ cp.0035
• Stanciu CN, Gnanasegaram SA. Don’t balk at using medical therapy to manage alcohol use disorder. Current Psychiatry. 2017;16(2):50-52.

Drug Brand Names

Acamprosate • Campral
Baclofen • Ozobax
Bupropion • Wellbutrin, Zyban
Disulfiram • Antabuse
Gabapentin • Neurontin
Lithium • Eskalith, Lithobid
Mirtazapine • Remeron
Naltrexone • ReVia, Vivitrol
Topiramate • Topamax

Off-label prescribing (OLP) refers to the practice of using medications for indications outside of those approved by the FDA, or in dosages, dose forms, or patient populations that have not been approved by the FDA.¹ OLP is common, occurring in many practice settings and nearly every medical specialty. In a 2006 review, Radley et al² found OLP accounted for 21% of the overall use of 160 common medications. The frequency of OLP varies between medication classes. Off-label use of anticonvulsants, antidepressants, and antipsychotics tends to be higher than that of other medications.^3,4 OLP is often more common in patient populations unlikely to be included in clinical trials due to ethical or logistical difficulties, such as pediatric patients and individuals who are pregnant. The Box summarizes several components that contribute to the prevalence of OLP and explains why this practice is often necessary for treating certain substance-related and addictive disorders.

Box

Several important medicolegal and ethical considerations surround OLP. The FDA prohibits off-label promotion, in which manufacturers advertise the use of a medication for off-label use.⁵ However, regulations allow physicians to use their best clinical judgment when prescribing medications for off-label use. When considering off-label use of any medication, physicians should review the most up-to-date research, including clinical trials, case reports, and reviews to safely support their decision-making. OLP should be guided by ethical principles such as autonomy, beneficence, nonmaleficence, and justice. Physicians should obtain informed consent by conducting an appropriate discussion of the risks, benefits, and alternatives of off-label medications. This conversation should be clearly documented, and physicians should provide written material regarding off-label options to patients when available. Finally, physicians should verify their patients’ understanding of this discussion, and allow patients to accept or decline off-label medications without pressure.

This article focuses on current and potential future medications available for OLP to treat patients with alcohol use disorder (AUD), gambling disorder (GD), stimulant use disorder, and cannabis use disorder.

Alcohol use disorder

CASE 1

Ms. X, age 67, has a history of severe AUD, mild renal impairment, and migraines. She presents to the outpatient clinic seeking help to drink less alcohol. Ms. X reports drinking 1 to 2 bottles of wine each day. She was previously treated for AUD but was not helped by naltrexone and did not tolerate disulfiram (abstinence was not her goal and she experienced significant adverse effects). Ms. X says she has a medical history of chronic migraines but denies other medical issues. The treatment team discusses alternative pharmacologic options, including acamprosate and topiramate. After outlining the dosing schedule and risks/benefits with Ms. X, you make the joint decision to start topiramate to reduce alcohol cravings and target her migraine symptoms.

Only 3 medications are FDA-approved for treating AUD: disulfiram, naltrexone (oral and injectable formulations), and acamprosate. Off-label options for AUD treatment include gabapentin, topiramate, and baclofen.

Gabapentin is FDA-approved for treating postherpetic neuralgia and partial seizures in patients age ≥3. The exact mechanism of action is unclear, though its effects are possibly related to its activity as a calcium channel ligand. It also carries a structural resemblance to gamma-aminobutyric acid (GABA), though it lacks activity at GABA receptors.

Several randomized controlled trials (RCTs) evaluating the efficacy of gabapentin for AUD produced promising results. In a comparison of gabapentin vs placebo for AUD, Anton et al⁶ found gabapentin led to significant increases in the number of participants with total alcohol abstinence and participants who reported reduced drinking. Notably, the effect was most prominent in those with heavy drinking patterns and pretreatment alcohol withdrawal symptoms. A total of 41% of participants with high alcohol withdrawal scores on pretreatment evaluation achieved total abstinence while taking gabapentin, compared to 1% in the placebo group.⁶ A meta-analysis of gabapentin for AUD by Kranzler et al⁷ included 7 RCTs and 32 effect measures. It found that although all outcome measures favored gabapentin over placebo, only the percentage of heavy drinking days was significantly different.

Gabapentin is dosed between 300 to 600 mg 3 times per day, but 1 study found that a higher dose (1,800 mg/d) was associated with better outcomes.⁸ Common adverse effects include sedation, dizziness, peripheral edema, and ataxia.

Continue to: Topiramate

Topiramate blocks voltage-gated sodium channels and enhances GABA-A receptor activity.⁹ It is indicated for the treatment of seizures, migraine prophylaxis, weight management, and weight loss. Several clinical trials, including RCTs,^10-12 demonstrated that topiramate was superior to placebo in reducing the percentage of heavy drinking days and overall drinking days. Some also showed that topiramate was associated with abstinence and reduced craving levels.^12,13 A meta-analysis by Blodgett et al¹⁴ found that compared to placebo, topiramate lowered the rate of heavy drinking and increased abstinence.

Topiramate is dosed from 50 to 150 mg twice daily, although some studies suggest a lower dose (≤75 mg/d) may be associated with clinical benefits.^15,16 One important clinical consideration: topiramate must follow a slow titration schedule (4 to 6 weeks) to increase tolerability and avoid adverse effects. Common adverse effects include sedation, word-finding difficulty, paresthesia, increased risk for renal calculi, dizziness, anorexia, and alterations in taste.

Baclofen is a GABA-B agonist FDA-approved for the treatment of muscle spasticity related to multiple sclerosis and reversible spasticity related to spinal cord lesions and multiple sclerosis. Of note, it is approved for treatment of AUD in Europe.

In a meta-analysis of 13 RCTs, Pierce et al¹⁷ found a greater likelihood of abstinence and greater time to first lapse of drinking with baclofen compared to placebo. Interestingly, a subgroup analysis found that the positive effects were limited to trials that used 30 to 60 mg/d of baclofen, and not evident in those that used higher doses. Additionally, there was no difference between baclofen and placebo with regard to several important outcomes, including alcohol cravings, anxiety, depression, or number of total abstinent days. A review by Andrade¹⁸ proposed that individualized treatment with high-dose baclofen (30 to 300 mg/d) may be a useful second-line approach in heavy drinkers who wish to reduce their alcohol intake.

Continue to: Before starting baclofen...

Before starting baclofen, patients should be informed about its adverse effects. Common adverse effects include sedation and motor impairment. More serious but less common adverse effects include seizures, respiratory depression with sleep apnea, severe mood disorders (ie, mania, depression, or suicide risk), and mental confusion. Baclofen should be gradually discontinued, because there is some risk of clinical withdrawal symptoms (ie, agitation, confusion, seizures, or delirium).

Among the medications discussed in this section, the evidence for gabapentin and topiramate is moderate to strong, while the evidence for baclofen is overall weaker or mixed. The American Psychiatric Association’s Practice Guideline suggests offering gabapentin or topiramate to patients with moderate to severe AUD whose goal is to achieve abstinence or reduce alcohol use, or those who prefer gabapentin or topiramate or cannot tolerate or have not responded to naltrexone and acamprosate.¹⁹ Clinicians must ensure patients have no contra­indications to the use of these medications. Due to the moderate quality evidence for a significant reduction in heavy drinking and increased abstinence,^14,20 a practice guideline from the US Department of Veterans Affairs and US Department of Defense²¹ recommends topiramate as 1 of 2 first-line treatments (the other is naltrexone). This guideline suggests gabapentin as a second-line treatment for AUD.²¹

Gambling disorder

CASE 2

Mr. P, age 28, seeks treatment for GD and cocaine use disorder. He reports a 7-year history of sports betting that has increasingly impaired his functioning over the past year. He lost his job, savings, and familial relationships due to his impulsive and risky behavior. Mr. P also reports frequent cocaine use, about 2 to 3 days per week, mostly on the weekends. The psychiatrist tells Mr. P there is no FDA-approved pharmacologic treatment for GD or cocaine use disorder. The psychiatrist discusses the option of naltrexone as off-label treatment for GD with the goal of reducing Mr. P’s urges to gamble, and points to possible benefits for cocaine use disorder.

GD impacts approximately 0.5% of the adult US population and is often co-occurring with substance use disorders.²² It is thought to share neurobiological and clinical similarities with substance use disorders.²³ There are currently no FDA-approved medications to treat the disorder. In studies of GD, treatment success with antidepressants and mood stabilizers has not been consistent,^23,24 but some promising results have been published for the opioid receptor antagonist naltrexone^24-29and N-acetylcysteine (NAC).^30-32

Naltrexone is thought to reduce gambling behavior and urges via downstream modulation of mesolimbic dopamine circuitry.²⁴ It is FDA-approved for the treatment of AUD and opioid use disorder. Open-label RCTs have found a reduction in gambling urges and behavior with daily naltrexone.^25-27 Dosing at 50 mg/d appears to be just as efficacious as higher doses such as 100 and 150 mg/d.²⁷ When used as a daily as-needed medication for strong gambling urges or if an individual was planning to gamble, naltrexone 50 mg/d was not effective.²⁸

Continue to: Naltrexone typically is started...

Naltrexone typically is started at 25 mg/d to assess tolerability and quickly titrated to 50 mg/d. When titrating, common adverse effects include nausea, vomiting, and transient elevations in transaminases. Another opioid antagonist, nalmefene, has also been studied in patients with GD. An RCT by Grant et al²⁹ that evaluated 207 patients found that compared with placebo, nalmefene 25 mg/d for 16 weeks was associated with a significant reduction in gambling assessment scores. In Europe, nalmefene is approved for treating AUD but the oral formulation is not currently available in the US.

N-acetylcysteine is thought to potentially reverse neuronal dysfunction seen in addictive disorders by glutamatergic modulation.³⁰ Research investigating NAC for GD is scarce. A pilot study found 16 of 27 patients with GD reduced gambling behavior with a mean dose of 1,476.9 mg/d.³¹ An additional study investigating the addition of NAC to behavioral therapy in nicotine-dependent individuals with pathologic gambling found a reduction in problem gambling after 18 weeks (6 weeks + 3 months follow-up).³² Common but mild adverse effects associated with NAC are nausea, vomiting, and diarrhea.

A meta-analysis by Goslar et al³³ that reviewed 34 studies (1,340 participants) found pharmacologic treatments were associated with large and medium pre-post reductions in global severity, frequency, and financial loss in patients with GD. RCTs studying opioid antagonists and mood stabilizers (combined with a cognitive intervention) as well as lithium for patients with comorbid bipolar disorder and GD demonstrated promising results.³³

Stimulant use disorder

There are no FDA-approved medications for stimulant use disorder. Multiple off-label options have been studied for the treatment of methamphetamine abuse and cocaine abuse.

Methamphetamine use has been expanding over the past decade with a 3.6-fold increase in positive methamphetamine screens in overdose deaths from 2011 to 2016.³⁴ Pharmacologic options studied for OLP of methamphetamine use disorder include mirtazapine, bupropion, naltrexone, and topiramate.

Continue to: Mirtazapine

Mirtazapine is an atypical antidepressant whose mechanism of action includes modulation of the serotonin, norepinephrine, and alpha-2 adrenergic systems. It is FDA-approved for the treatment of major depressive disorder (MDD). In a randomized placebo-controlled study, mirtazapine 30 mg/d at night was found to decrease methamphetamine use for active users and led to decreased sexual risk in men who have sex with men.³⁵ These results were supported by an additional RCT in which mirtazapine 30 mg/d significantly reduced rates of methamphetamine use vs placebo at 24 and 36 weeks despite poor medication adherence.³⁶ Adverse effects to monitor in patients treated with mirtazapine include increased appetite, weight gain, sedation, and constipation.

Bupropion is a norepinephrine dopamine reuptake inhibitor that produces increased neurotransmission of norepinephrine and dopamine in the CNS. It is FDA-approved for the treatment of MDD and as an aid for smoking cessation. Bupropion has been studied for methamphetamine use disorder with mixed results. In a randomized placebo-controlled trial, bupropion sustained release 150 mg twice daily was not more effective than placebo in reducing methamphetamine use.³⁷ However, the extended-release formulation of bupropion 450 mg/d combined with long-acting injectable naltrexone was associated with a reduction in methamphetamine use over 12 weeks.³⁸ Bupropion is generally well tolerated; common adverse effects include insomnia, tremor, headache, and dizziness.

Naltrexone. Data about using oral naltrexone to treat stimulant use disorders are limited. A randomized, placebo-controlled trial by Jayaram-Lindström et al³⁹ found naltrexone 50 mg/d significantly reduced amphetamine use compared to placebo. Additionally, naltrexone 50 and 150 mg/d have been shown to reduce cocaine use over time in combination with therapy for cocaine-dependent patients and those dependent on alcohol and cocaine.^40,41

Topiramate has been studied for the treatment of cocaine use disorder. It is hypothesized that modulation of the mesocorticolimbic dopamine system may contribute to decreased cocaine cravings.⁴² A pilot study by Kampman et al⁴³ found that after an 8-week titration of topiramate to 200 mg/d, individuals were more likely to achieve cocaine abstinence compared to those who receive placebo. In an RCT, Elkashef et al⁴⁴ did not find topiramate assisted with increased abstinence of methamphetamine in active users at a target dose of 200 mg/d. However, it was associated with reduced relapse rates in individuals who were abstinent prior to the study.⁴⁴ At a target dose of 300 mg/d, topiramate also outperformed placebo in decreasing days of cocaine use.⁴² Adverse effects of topiramate included paresthesia, alteration in taste, and difficulty with concentration.

Cannabis use disorder

In recent years, cannabis use in the US has greatly increased⁴⁵ but no medications are FDA-approved for treating cannabis use disorder. Studies of pharmacologic options for cannabis use disorder have had mixed results.⁴⁶ A meta-analysis by Bahji et al⁴⁷ of 24 studies investigating pharmacotherapies for cannabis use disorder highlighted the lack of adequate evidence. In this section, we focus on a few positive trials of NAC and gabapentin.

Continue to: N-acetylcysteine

N-acetylcysteine. Studies investigating NAC 1,200 mg twice daily have been promising in adolescent and adult populations.^48-50 There are some mixed results, however. A large RCT found NAC 1,200 mg twice daily was not better than placebo in helping adults achieve abstinence from cannabis.⁵¹

Gabapentin may be a viable option for treating cannabis use disorder. A pilot study by Mason et al⁵² found gabapentin 1,200 mg/d was more effective than placebo at reducing cannabis use among treatment-seeking adults.

When and how to consider OLP

OLP for addictive disorders is common and often necessary. This is primarily due to limitations of the FDA-approved medications and because there are no FDA-approved medications for many substance-related and addictive disorders (ie, GD, cannabis use disorder, and stimulant use disorder). When assessing pharmacotherapy options, if FDA-approved medications are available for certain diagnoses, clinicians should first consider them. The off-label medications discussed in this article are outlined in the Table.^{6-21,24-28,30-33,35-44,48-52}

The overall level of evidence to support the use of off-label medications is lower than that of FDA-approved medications, which contributes to potential medicolegal concerns of OLP. Off-label medications should be considered when there are no FDA-approved medications available, and the decision to use off-label medications should be based on evidence from the literature and current standard of care. Additionally, OLP is necessary if a patient cannot tolerate FDA-approved medications, is not helped by FDA-approved treatments, or when there are other clinical reasons to choose a particular off-label medication. For example, if a patient has comorbid AUD and obesity (or migraines), using topiramate may be appropriate because it may target alcohol cravings and can be helpful for weight loss (and migraine prophylaxis). Similarly, for patients with AUD and neuropathic pain, using gabapentin can be considered for its dual therapeutic effects.

It is critical for clinicians to understand the landscape of off-label options for treating addictive disorders. Additional research in the form of RCTs is needed to better clarify the efficacy and adverse effects of these treatments.

Continue to: Bottom Line

Off-label prescribing is prevalent in practice, including in the treatment of substance-related and addictive disorders. When considering off-label use of any medication, clinicians should review the most recent research, obtain informed consent from patients, and verify patients’ understanding of the potential risks and adverse effects associated with the particular medication.

Related Resources

• Joshi KG, Frierson RL. Off-label prescribing: how to limit your liability. Current Psychiatry. 2020;19(9):12,39. doi:10.12788/ cp.0035
• Stanciu CN, Gnanasegaram SA. Don’t balk at using medical therapy to manage alcohol use disorder. Current Psychiatry. 2017;16(2):50-52.

Drug Brand Names

Acamprosate • Campral
Baclofen • Ozobax
Bupropion • Wellbutrin, Zyban
Disulfiram • Antabuse
Gabapentin • Neurontin
Lithium • Eskalith, Lithobid
Mirtazapine • Remeron
Naltrexone • ReVia, Vivitrol
Topiramate • Topamax

Off-label prescribing (OLP) refers to the practice of using medications for indications outside of those approved by the FDA, or in dosages, dose forms, or patient populations that have not been approved by the FDA.¹ OLP is common, occurring in many practice settings and nearly every medical specialty. In a 2006 review, Radley et al² found OLP accounted for 21% of the overall use of 160 common medications. The frequency of OLP varies between medication classes. Off-label use of anticonvulsants, antidepressants, and antipsychotics tends to be higher than that of other medications.^3,4 OLP is often more common in patient populations unlikely to be included in clinical trials due to ethical or logistical difficulties, such as pediatric patients and individuals who are pregnant. The Box summarizes several components that contribute to the prevalence of OLP and explains why this practice is often necessary for treating certain substance-related and addictive disorders.

Box

Several important medicolegal and ethical considerations surround OLP. The FDA prohibits off-label promotion, in which manufacturers advertise the use of a medication for off-label use.⁵ However, regulations allow physicians to use their best clinical judgment when prescribing medications for off-label use. When considering off-label use of any medication, physicians should review the most up-to-date research, including clinical trials, case reports, and reviews to safely support their decision-making. OLP should be guided by ethical principles such as autonomy, beneficence, nonmaleficence, and justice. Physicians should obtain informed consent by conducting an appropriate discussion of the risks, benefits, and alternatives of off-label medications. This conversation should be clearly documented, and physicians should provide written material regarding off-label options to patients when available. Finally, physicians should verify their patients’ understanding of this discussion, and allow patients to accept or decline off-label medications without pressure.

This article focuses on current and potential future medications available for OLP to treat patients with alcohol use disorder (AUD), gambling disorder (GD), stimulant use disorder, and cannabis use disorder.

Alcohol use disorder

CASE 1

Ms. X, age 67, has a history of severe AUD, mild renal impairment, and migraines. She presents to the outpatient clinic seeking help to drink less alcohol. Ms. X reports drinking 1 to 2 bottles of wine each day. She was previously treated for AUD but was not helped by naltrexone and did not tolerate disulfiram (abstinence was not her goal and she experienced significant adverse effects). Ms. X says she has a medical history of chronic migraines but denies other medical issues. The treatment team discusses alternative pharmacologic options, including acamprosate and topiramate. After outlining the dosing schedule and risks/benefits with Ms. X, you make the joint decision to start topiramate to reduce alcohol cravings and target her migraine symptoms.

Only 3 medications are FDA-approved for treating AUD: disulfiram, naltrexone (oral and injectable formulations), and acamprosate. Off-label options for AUD treatment include gabapentin, topiramate, and baclofen.

Gabapentin is FDA-approved for treating postherpetic neuralgia and partial seizures in patients age ≥3. The exact mechanism of action is unclear, though its effects are possibly related to its activity as a calcium channel ligand. It also carries a structural resemblance to gamma-aminobutyric acid (GABA), though it lacks activity at GABA receptors.

Several randomized controlled trials (RCTs) evaluating the efficacy of gabapentin for AUD produced promising results. In a comparison of gabapentin vs placebo for AUD, Anton et al⁶ found gabapentin led to significant increases in the number of participants with total alcohol abstinence and participants who reported reduced drinking. Notably, the effect was most prominent in those with heavy drinking patterns and pretreatment alcohol withdrawal symptoms. A total of 41% of participants with high alcohol withdrawal scores on pretreatment evaluation achieved total abstinence while taking gabapentin, compared to 1% in the placebo group.⁶ A meta-analysis of gabapentin for AUD by Kranzler et al⁷ included 7 RCTs and 32 effect measures. It found that although all outcome measures favored gabapentin over placebo, only the percentage of heavy drinking days was significantly different.

Gabapentin is dosed between 300 to 600 mg 3 times per day, but 1 study found that a higher dose (1,800 mg/d) was associated with better outcomes.⁸ Common adverse effects include sedation, dizziness, peripheral edema, and ataxia.

Continue to: Topiramate

Topiramate blocks voltage-gated sodium channels and enhances GABA-A receptor activity.⁹ It is indicated for the treatment of seizures, migraine prophylaxis, weight management, and weight loss. Several clinical trials, including RCTs,^10-12 demonstrated that topiramate was superior to placebo in reducing the percentage of heavy drinking days and overall drinking days. Some also showed that topiramate was associated with abstinence and reduced craving levels.^12,13 A meta-analysis by Blodgett et al¹⁴ found that compared to placebo, topiramate lowered the rate of heavy drinking and increased abstinence.

Topiramate is dosed from 50 to 150 mg twice daily, although some studies suggest a lower dose (≤75 mg/d) may be associated with clinical benefits.^15,16 One important clinical consideration: topiramate must follow a slow titration schedule (4 to 6 weeks) to increase tolerability and avoid adverse effects. Common adverse effects include sedation, word-finding difficulty, paresthesia, increased risk for renal calculi, dizziness, anorexia, and alterations in taste.

Baclofen is a GABA-B agonist FDA-approved for the treatment of muscle spasticity related to multiple sclerosis and reversible spasticity related to spinal cord lesions and multiple sclerosis. Of note, it is approved for treatment of AUD in Europe.

In a meta-analysis of 13 RCTs, Pierce et al¹⁷ found a greater likelihood of abstinence and greater time to first lapse of drinking with baclofen compared to placebo. Interestingly, a subgroup analysis found that the positive effects were limited to trials that used 30 to 60 mg/d of baclofen, and not evident in those that used higher doses. Additionally, there was no difference between baclofen and placebo with regard to several important outcomes, including alcohol cravings, anxiety, depression, or number of total abstinent days. A review by Andrade¹⁸ proposed that individualized treatment with high-dose baclofen (30 to 300 mg/d) may be a useful second-line approach in heavy drinkers who wish to reduce their alcohol intake.

Continue to: Before starting baclofen...

Before starting baclofen, patients should be informed about its adverse effects. Common adverse effects include sedation and motor impairment. More serious but less common adverse effects include seizures, respiratory depression with sleep apnea, severe mood disorders (ie, mania, depression, or suicide risk), and mental confusion. Baclofen should be gradually discontinued, because there is some risk of clinical withdrawal symptoms (ie, agitation, confusion, seizures, or delirium).

Among the medications discussed in this section, the evidence for gabapentin and topiramate is moderate to strong, while the evidence for baclofen is overall weaker or mixed. The American Psychiatric Association’s Practice Guideline suggests offering gabapentin or topiramate to patients with moderate to severe AUD whose goal is to achieve abstinence or reduce alcohol use, or those who prefer gabapentin or topiramate or cannot tolerate or have not responded to naltrexone and acamprosate.¹⁹ Clinicians must ensure patients have no contra­indications to the use of these medications. Due to the moderate quality evidence for a significant reduction in heavy drinking and increased abstinence,^14,20 a practice guideline from the US Department of Veterans Affairs and US Department of Defense²¹ recommends topiramate as 1 of 2 first-line treatments (the other is naltrexone). This guideline suggests gabapentin as a second-line treatment for AUD.²¹

Gambling disorder

CASE 2

Mr. P, age 28, seeks treatment for GD and cocaine use disorder. He reports a 7-year history of sports betting that has increasingly impaired his functioning over the past year. He lost his job, savings, and familial relationships due to his impulsive and risky behavior. Mr. P also reports frequent cocaine use, about 2 to 3 days per week, mostly on the weekends. The psychiatrist tells Mr. P there is no FDA-approved pharmacologic treatment for GD or cocaine use disorder. The psychiatrist discusses the option of naltrexone as off-label treatment for GD with the goal of reducing Mr. P’s urges to gamble, and points to possible benefits for cocaine use disorder.

GD impacts approximately 0.5% of the adult US population and is often co-occurring with substance use disorders.²² It is thought to share neurobiological and clinical similarities with substance use disorders.²³ There are currently no FDA-approved medications to treat the disorder. In studies of GD, treatment success with antidepressants and mood stabilizers has not been consistent,^23,24 but some promising results have been published for the opioid receptor antagonist naltrexone^24-29and N-acetylcysteine (NAC).^30-32

Naltrexone is thought to reduce gambling behavior and urges via downstream modulation of mesolimbic dopamine circuitry.²⁴ It is FDA-approved for the treatment of AUD and opioid use disorder. Open-label RCTs have found a reduction in gambling urges and behavior with daily naltrexone.^25-27 Dosing at 50 mg/d appears to be just as efficacious as higher doses such as 100 and 150 mg/d.²⁷ When used as a daily as-needed medication for strong gambling urges or if an individual was planning to gamble, naltrexone 50 mg/d was not effective.²⁸

Continue to: Naltrexone typically is started...

Naltrexone typically is started at 25 mg/d to assess tolerability and quickly titrated to 50 mg/d. When titrating, common adverse effects include nausea, vomiting, and transient elevations in transaminases. Another opioid antagonist, nalmefene, has also been studied in patients with GD. An RCT by Grant et al²⁹ that evaluated 207 patients found that compared with placebo, nalmefene 25 mg/d for 16 weeks was associated with a significant reduction in gambling assessment scores. In Europe, nalmefene is approved for treating AUD but the oral formulation is not currently available in the US.

N-acetylcysteine is thought to potentially reverse neuronal dysfunction seen in addictive disorders by glutamatergic modulation.³⁰ Research investigating NAC for GD is scarce. A pilot study found 16 of 27 patients with GD reduced gambling behavior with a mean dose of 1,476.9 mg/d.³¹ An additional study investigating the addition of NAC to behavioral therapy in nicotine-dependent individuals with pathologic gambling found a reduction in problem gambling after 18 weeks (6 weeks + 3 months follow-up).³² Common but mild adverse effects associated with NAC are nausea, vomiting, and diarrhea.

A meta-analysis by Goslar et al³³ that reviewed 34 studies (1,340 participants) found pharmacologic treatments were associated with large and medium pre-post reductions in global severity, frequency, and financial loss in patients with GD. RCTs studying opioid antagonists and mood stabilizers (combined with a cognitive intervention) as well as lithium for patients with comorbid bipolar disorder and GD demonstrated promising results.³³

Stimulant use disorder

There are no FDA-approved medications for stimulant use disorder. Multiple off-label options have been studied for the treatment of methamphetamine abuse and cocaine abuse.

Methamphetamine use has been expanding over the past decade with a 3.6-fold increase in positive methamphetamine screens in overdose deaths from 2011 to 2016.³⁴ Pharmacologic options studied for OLP of methamphetamine use disorder include mirtazapine, bupropion, naltrexone, and topiramate.

Continue to: Mirtazapine

Mirtazapine is an atypical antidepressant whose mechanism of action includes modulation of the serotonin, norepinephrine, and alpha-2 adrenergic systems. It is FDA-approved for the treatment of major depressive disorder (MDD). In a randomized placebo-controlled study, mirtazapine 30 mg/d at night was found to decrease methamphetamine use for active users and led to decreased sexual risk in men who have sex with men.³⁵ These results were supported by an additional RCT in which mirtazapine 30 mg/d significantly reduced rates of methamphetamine use vs placebo at 24 and 36 weeks despite poor medication adherence.³⁶ Adverse effects to monitor in patients treated with mirtazapine include increased appetite, weight gain, sedation, and constipation.

Bupropion is a norepinephrine dopamine reuptake inhibitor that produces increased neurotransmission of norepinephrine and dopamine in the CNS. It is FDA-approved for the treatment of MDD and as an aid for smoking cessation. Bupropion has been studied for methamphetamine use disorder with mixed results. In a randomized placebo-controlled trial, bupropion sustained release 150 mg twice daily was not more effective than placebo in reducing methamphetamine use.³⁷ However, the extended-release formulation of bupropion 450 mg/d combined with long-acting injectable naltrexone was associated with a reduction in methamphetamine use over 12 weeks.³⁸ Bupropion is generally well tolerated; common adverse effects include insomnia, tremor, headache, and dizziness.

Naltrexone. Data about using oral naltrexone to treat stimulant use disorders are limited. A randomized, placebo-controlled trial by Jayaram-Lindström et al³⁹ found naltrexone 50 mg/d significantly reduced amphetamine use compared to placebo. Additionally, naltrexone 50 and 150 mg/d have been shown to reduce cocaine use over time in combination with therapy for cocaine-dependent patients and those dependent on alcohol and cocaine.^40,41

Topiramate has been studied for the treatment of cocaine use disorder. It is hypothesized that modulation of the mesocorticolimbic dopamine system may contribute to decreased cocaine cravings.⁴² A pilot study by Kampman et al⁴³ found that after an 8-week titration of topiramate to 200 mg/d, individuals were more likely to achieve cocaine abstinence compared to those who receive placebo. In an RCT, Elkashef et al⁴⁴ did not find topiramate assisted with increased abstinence of methamphetamine in active users at a target dose of 200 mg/d. However, it was associated with reduced relapse rates in individuals who were abstinent prior to the study.⁴⁴ At a target dose of 300 mg/d, topiramate also outperformed placebo in decreasing days of cocaine use.⁴² Adverse effects of topiramate included paresthesia, alteration in taste, and difficulty with concentration.

Cannabis use disorder

In recent years, cannabis use in the US has greatly increased⁴⁵ but no medications are FDA-approved for treating cannabis use disorder. Studies of pharmacologic options for cannabis use disorder have had mixed results.⁴⁶ A meta-analysis by Bahji et al⁴⁷ of 24 studies investigating pharmacotherapies for cannabis use disorder highlighted the lack of adequate evidence. In this section, we focus on a few positive trials of NAC and gabapentin.

Continue to: N-acetylcysteine

N-acetylcysteine. Studies investigating NAC 1,200 mg twice daily have been promising in adolescent and adult populations.^48-50 There are some mixed results, however. A large RCT found NAC 1,200 mg twice daily was not better than placebo in helping adults achieve abstinence from cannabis.⁵¹

Gabapentin may be a viable option for treating cannabis use disorder. A pilot study by Mason et al⁵² found gabapentin 1,200 mg/d was more effective than placebo at reducing cannabis use among treatment-seeking adults.

When and how to consider OLP

OLP for addictive disorders is common and often necessary. This is primarily due to limitations of the FDA-approved medications and because there are no FDA-approved medications for many substance-related and addictive disorders (ie, GD, cannabis use disorder, and stimulant use disorder). When assessing pharmacotherapy options, if FDA-approved medications are available for certain diagnoses, clinicians should first consider them. The off-label medications discussed in this article are outlined in the Table.^{6-21,24-28,30-33,35-44,48-52}

The overall level of evidence to support the use of off-label medications is lower than that of FDA-approved medications, which contributes to potential medicolegal concerns of OLP. Off-label medications should be considered when there are no FDA-approved medications available, and the decision to use off-label medications should be based on evidence from the literature and current standard of care. Additionally, OLP is necessary if a patient cannot tolerate FDA-approved medications, is not helped by FDA-approved treatments, or when there are other clinical reasons to choose a particular off-label medication. For example, if a patient has comorbid AUD and obesity (or migraines), using topiramate may be appropriate because it may target alcohol cravings and can be helpful for weight loss (and migraine prophylaxis). Similarly, for patients with AUD and neuropathic pain, using gabapentin can be considered for its dual therapeutic effects.

It is critical for clinicians to understand the landscape of off-label options for treating addictive disorders. Additional research in the form of RCTs is needed to better clarify the efficacy and adverse effects of these treatments.

Continue to: Bottom Line

Off-label prescribing is prevalent in practice, including in the treatment of substance-related and addictive disorders. When considering off-label use of any medication, clinicians should review the most recent research, obtain informed consent from patients, and verify patients’ understanding of the potential risks and adverse effects associated with the particular medication.

Related Resources

• Joshi KG, Frierson RL. Off-label prescribing: how to limit your liability. Current Psychiatry. 2020;19(9):12,39. doi:10.12788/ cp.0035
• Stanciu CN, Gnanasegaram SA. Don’t balk at using medical therapy to manage alcohol use disorder. Current Psychiatry. 2017;16(2):50-52.

Drug Brand Names

Acamprosate • Campral
Baclofen • Ozobax
Bupropion • Wellbutrin, Zyban
Disulfiram • Antabuse
Gabapentin • Neurontin
Lithium • Eskalith, Lithobid
Mirtazapine • Remeron
Naltrexone • ReVia, Vivitrol
Topiramate • Topamax

Burnout is an occupational phenomenon and a syndrome resulting from unsuccessfully managed chronic workplace stress. The characteristic features of burnout include feelings of exhaustion, cynicism, and reduced professional efficacy.¹ A career in surgery is associated with demanding and unpredictable work hours in a high-stress environment.^2-8 Research indicates that surgeons are at an elevated risk for developing burnout and mental health problems that can compromise patient care. A survey of the fellows of the American College of Surgeons found that 40% of surgeons experience burnout, 30% experience symptoms of depression, and 28% have a mental quality of life (QOL) score greater than one-half an SD below the population norm.^9,10 Surgeon burnout was also found to compromise the delivery of medical care.^9,10

To prevent serious harm to surgeons and patients, it is critical to understand the causative factors of burnout among surgeons and how they can be addressed. We conducted this systematic review to identify factors linked to burnout across surgical specialties and to suggest ways to mitigate these risk factors.  

Methods

To identify studies of burnout among surgeons, we conducted an electronic search of Ovid MEDLINE, Ovid PsycInfo, SCOPUS, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials. The headings and keywords used are listed in Supplemental Table 1. Studies met the inclusion criteria if they evaluated residents or attendings, used a tool to measure burnout, and examined any surgical specialty. Studies were excluded if they were published before 2010; were conducted outside the United States; were review articles, commentaries, or abstracts without full text articles; evaluated medical school students; were published in a language other than English; did not use a tool to measure burnout; or examined a nonsurgical specialty.  Our analysis was guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)¹¹ and is outlined in the Supplemental Figure.

Results

Surgical specialties and burnout

We identified 56 studies^2-10,12-58 that focused on specific surgical specialties in relation to burnout. Supplemental Table 2^2-10,12-58 lists these studies and the surgical specialties they evaluated.

Work/life balance factors

Fifteen studies^{2-5,14,15,18,19,22,32,34,38,39,47,57} examined the role of work/life balance in burnout. Table 1^{2-5,14,15,18,19,22,32,34,38,39,47,57} lists the work/life factors these studies identified as being linked to burnout. Six studies^{2,4,18,22,32,47} discussed how decreased leisure time was linked to burnout. Eleven studies^{2,4,14,15,19,22,34,38,39,42,57} associated inabilities to meet family commitments with burnout. A lack of time to spend with family and not having adequate time to raise children was more prevalent among women. Seven studies^{2,3,18,22,32,34,47} implicated increased time commitment to work as playing a role in burnout. This increased time commitment was also found to be a compounding variable for other factors, such as limited time for family and leisure.

Work hours

Fifteen studies^{2,7,14,20,21,30,34,41,42,44-46,50,52,56} examined work hours and burnout. Of these, 14^{2,7,14,20,21,30,34,42,44-46,50,52,56} found a correlation between increased work hours and burnout, while only 1 study⁴¹ found no correlation between these factors. 

Medical errors

Six studies^{2,14,18,43,49,52} discussed the role of burnout in medical errors. Of these, 5^{2,14,43,49,52} reported a correlation between burnout and medical errors, while 1 study¹⁸ found no link between burnout and medical errors. The medical errors were self-reported.^14,49 They included actions that resulted in patient harm, sample collection error, and errors in medication orders and laboratory test orders.²

Continue to: Institutional and organizational factors

Eighteen studies^{3,13,14,18,20,22,23,29,30,36-38,44,45,47,54,56,57} examined how different organizational factors play a role in burnout. Four studies^3,13,20,37 discussed administrative/bureaucratic work, 4^20,45,54,57 mentioned electronic medical documentation, 2^22,30 covered duty hour regulations, 3^18,45,57 discussed mistreatment of physicians, and 6^{13,18,23,44,47,56} described the importance of workplace support in addressing burnout.

Physical and mental health factors

Eighteen studies^{6,7,14,15,17,20,26,27,29,34,43,44,48,52,54,57-59} discussed aspects of physical and mental health linked to burnout. Among these, 3^34,43,59 discussed the importance of physical health and focused on how improving physical health can reduce stress and burnout. Three studies^6,17,58 noted the prevalence of suicidal ideation in both residents and attendings experiencing prolonged burnout. Five studies^{26,29,43,44,48} described the systematic barriers that inhibit physicians from getting professional help. Two studies^7,27 reported marital status as a factor for burnout; participants who were single reported higher levels of depression and suicidal ideation. Five studies^{6,14,15,54,57} outlined how depression is associated with burnout.

Strategies to mitigate burnout

Fifteen studies^{2,4,5,14,20,22,33,36,47,51,53,55-58} described strategies physicians use to cope with burnout. Table 2^{2,4,5,14,20,22,33,36,47,51,53,55-58} outlines the strategies postulated and reported by these studies as helpful in reducing burnout. Two studies^2,4 mentioned that physicians may turn to maladaptive behaviors, such as substance abuse, to cope with stress and burnout. Four studies^2,4,53,56 mentioned the importance of social support in fighting burnout and building resilience. Ten studies^{2,5,14,20,22,33,36,47,57,58} described the benefits of institutional interventions, such as what administrators can do to reduce the rate of burnout. Three studies^5,36,53 postulated different adaptive behaviors physicians can implement to reduce burnout.

Take-home points 

Research that focused on work/life balance and burnout found excessive time commitment to work is a major factor associated with poor work/life balance. Residents who worked >80 hours a week had a significantly higher burnout rate.⁵⁶ One study found that 70% of residents reported not getting enough sleep, 30% reported not having enough energy for relationships, and 39% reported that they were not eating or exercising due to time constraints.⁴ A high correlation was found between the number of hours worked per week and rates of burnout, emotional exhaustion, and depersonalization. Emotional exhaustion and depersonalization are aspects of burnout measured by the Maslach Burnout Inventory (MBI).²⁴ The excessive time commitment to work not only contributes to burnout but also prevents physicians from getting professional help. In 1 study, both residents (56%) and attendings (24%) reported that 1 of the biggest barriers to getting help for their burnout symptoms was the inability to take time off.³⁴ Research indicates that the hours worked per week and work/home conflicts were independently associated with burnout and career satisfaction.¹⁵ A decrease of weekly work hours may give physicians time to meet their responsibilities at work and home, allowing for a decrease in burnout and an increase in career satisfaction.

Increased work hours have also been found to be correlated with medical errors. One study found that those who worked 60 hours per week were significantly less likely to report any major medical errors in the previous 3 months compared with those who worked 80 hours per week.⁹ The risk for the number of medical errors has been reported as being 2-fold if surgeons are unable to combat the burnout.⁴⁹ On the other hand, a positive and supportive environment with easy access to resources to combat burnout and burnout prevention programs can reduce the frequency of medical errors, which also can reduce the risk of malpractice, thus further reducing stress and burnout.⁴³

Continue to: In response to resident complaints...

In response to resident complaints about long duty hours, a new rule has been implemented that states residents cannot work >16 hours per shift.³⁰ This rule has been found to increase quality of life and prevent burnout.³⁰

The amount of time spent on electronic medical records and documentation has been a major complaint from doctors and was identified as a factor contributing to burnout.⁴⁵ It can act as a time drain that impedes the physician from providing optimal patient care and cause additional stress. This suggests the need for organizations to find solutions to minimize this strain.

A concerning issue reported as an institutional factor and associated with burnout is mistreatment through discrimination, harassment, and physical or verbal abuse. A recent study found 45% of general and vascular surgeons reported being mistreated in some fashion.⁵⁷ The strategies reported as helpful for institutions to combat mistreatment include resilience training, improved mentorship, and implicit bias training.⁵⁷

Burnout has been positively correlated with anxiety and depression.⁶ A recent study reported that 13% of orthopedic surgery residents screened positive for depression.⁴⁴ Higher levels of burnout and depersonalization have been found to be closely associated with increased rates of suicidal ideation.¹⁷ In a study of vascular surgeons, 8% were found to report suicidal ideation, and this increased to 15% among vascular surgeons who had higher levels of depersonalization and emotional exhaustion,⁵⁸ both of which are associated with burnout. In another study, surgery residents and fellows were found to have lower levels of personal achievement and higher levels of depersonalization, depressive symptoms, alcohol abuse, and suicidal ideation compared to attending physicians and the general population.⁵⁴ These findings spell out the association between burnout and depressive symptoms among surgeons and emphasize the need for institutions to create a culture that supports the mental health needs of their physicians. Without access to supportive resources, residents resort to alternative methods that may be detrimental in the long run. In a recent study, 17% of residents admitted to using alcohol, including binge drinking, to cope with their stress.⁴

Burnout and depression are linked to physical health risks such as cardiovascular disease, diabetes, substance abuse, and male infertility.⁶ Exercise has been shown to be beneficial for stress reduction, which can lead to changes in metabolism, inflammation, coagulation, and autonomic function.⁶ One study of surgeons found aerobic exercise and strength training were associated with lower rates of burnout and a higher quality of life.⁵⁹

Continue to: The amount of burnout physicians...

The amount of burnout physicians experience can be determined by how they respond to adversities. Adaptive behaviors such as socializing, mindfulness, volunteering, and exercising have been found to be protective against burnout.^6,37,54 Resilience training and maintaining low stress at work can decrease burnout.³⁷ These findings highlight the need for physicians to be trained in the appropriate ways to combat their burnout symptoms.

Unfortunately, seeking help by health care professionals to improve mental health has been stigmatized, causing physicians to not seek help and instead resort to other ways to cope with their distress.^26,34 While some of these coping methods may be positive, others—such as substance abuse or stress eating—can be maladaptive, leading to a poor quality of life, and in some cases, suicide.⁵⁴ It is vital that effective mental health services become more accessible and for health care professionals to become aware of their maladaptive behaviors.³⁴

Institutions finding ways to ease the path for their physicians to seek professional help to combat burnout may mitigate its negative impact. One strategy is to embed access to mental health services within regular wellness checks. Institutions can use wellness checks to provide resources to physicians who need it. These interventions have been found to be effective because they give physicians a safe space to seek help and become aware of any factors that could lead to burnout.¹⁸ Apart from these direct attempts to combat burnout, program-sponsored social events would also promote social connectedness with colleagues and contribute to a sense of well-being that could help decrease levels of burnout and depression.¹³ Mentorship has been shown to play a crucial role in decreasing burnout among residents. One study that examined the role of mentorship reported that 55% of residents felt supported, and of these, 96% felt mentorship was critical to their success.¹⁸ The role of institutions in helping to improve the well-being of surgeons is highlighted by the finding that increasing workplace support results in psychological resilience that can mitigate burnout at its roots.²⁹

Bottom Line

Surgeons are at risk for burnout, which can impact their mental health and reduce their professional efficacy. Both institutions and surgeons themselves can take action to prevent burnout and treat burnout early when it occurs.

Related Resources

• Pahal P, Lippmann S. Building a better work/life balance. Current Psychiatry. 2021;20(8):e1-e2. doi:10.12788/cp.0158
• Gibson R, Hategan A. Physician burnout vs depression: recognize the signs. Current Psychiatry. 2019;18(10):41-42.

Burnout is an occupational phenomenon and a syndrome resulting from unsuccessfully managed chronic workplace stress. The characteristic features of burnout include feelings of exhaustion, cynicism, and reduced professional efficacy.¹ A career in surgery is associated with demanding and unpredictable work hours in a high-stress environment.^2-8 Research indicates that surgeons are at an elevated risk for developing burnout and mental health problems that can compromise patient care. A survey of the fellows of the American College of Surgeons found that 40% of surgeons experience burnout, 30% experience symptoms of depression, and 28% have a mental quality of life (QOL) score greater than one-half an SD below the population norm.^9,10 Surgeon burnout was also found to compromise the delivery of medical care.^9,10

To prevent serious harm to surgeons and patients, it is critical to understand the causative factors of burnout among surgeons and how they can be addressed. We conducted this systematic review to identify factors linked to burnout across surgical specialties and to suggest ways to mitigate these risk factors.  

Methods

To identify studies of burnout among surgeons, we conducted an electronic search of Ovid MEDLINE, Ovid PsycInfo, SCOPUS, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials. The headings and keywords used are listed in Supplemental Table 1. Studies met the inclusion criteria if they evaluated residents or attendings, used a tool to measure burnout, and examined any surgical specialty. Studies were excluded if they were published before 2010; were conducted outside the United States; were review articles, commentaries, or abstracts without full text articles; evaluated medical school students; were published in a language other than English; did not use a tool to measure burnout; or examined a nonsurgical specialty.  Our analysis was guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)¹¹ and is outlined in the Supplemental Figure.

Results

Surgical specialties and burnout

We identified 56 studies^2-10,12-58 that focused on specific surgical specialties in relation to burnout. Supplemental Table 2^2-10,12-58 lists these studies and the surgical specialties they evaluated.

Work/life balance factors

Fifteen studies^{2-5,14,15,18,19,22,32,34,38,39,47,57} examined the role of work/life balance in burnout. Table 1^{2-5,14,15,18,19,22,32,34,38,39,47,57} lists the work/life factors these studies identified as being linked to burnout. Six studies^{2,4,18,22,32,47} discussed how decreased leisure time was linked to burnout. Eleven studies^{2,4,14,15,19,22,34,38,39,42,57} associated inabilities to meet family commitments with burnout. A lack of time to spend with family and not having adequate time to raise children was more prevalent among women. Seven studies^{2,3,18,22,32,34,47} implicated increased time commitment to work as playing a role in burnout. This increased time commitment was also found to be a compounding variable for other factors, such as limited time for family and leisure.

Work hours

Fifteen studies^{2,7,14,20,21,30,34,41,42,44-46,50,52,56} examined work hours and burnout. Of these, 14^{2,7,14,20,21,30,34,42,44-46,50,52,56} found a correlation between increased work hours and burnout, while only 1 study⁴¹ found no correlation between these factors. 

Medical errors

Six studies^{2,14,18,43,49,52} discussed the role of burnout in medical errors. Of these, 5^{2,14,43,49,52} reported a correlation between burnout and medical errors, while 1 study¹⁸ found no link between burnout and medical errors. The medical errors were self-reported.^14,49 They included actions that resulted in patient harm, sample collection error, and errors in medication orders and laboratory test orders.²

Continue to: Institutional and organizational factors

Eighteen studies^{3,13,14,18,20,22,23,29,30,36-38,44,45,47,54,56,57} examined how different organizational factors play a role in burnout. Four studies^3,13,20,37 discussed administrative/bureaucratic work, 4^20,45,54,57 mentioned electronic medical documentation, 2^22,30 covered duty hour regulations, 3^18,45,57 discussed mistreatment of physicians, and 6^{13,18,23,44,47,56} described the importance of workplace support in addressing burnout.

Physical and mental health factors

Eighteen studies^{6,7,14,15,17,20,26,27,29,34,43,44,48,52,54,57-59} discussed aspects of physical and mental health linked to burnout. Among these, 3^34,43,59 discussed the importance of physical health and focused on how improving physical health can reduce stress and burnout. Three studies^6,17,58 noted the prevalence of suicidal ideation in both residents and attendings experiencing prolonged burnout. Five studies^{26,29,43,44,48} described the systematic barriers that inhibit physicians from getting professional help. Two studies^7,27 reported marital status as a factor for burnout; participants who were single reported higher levels of depression and suicidal ideation. Five studies^{6,14,15,54,57} outlined how depression is associated with burnout.

Strategies to mitigate burnout

Fifteen studies^{2,4,5,14,20,22,33,36,47,51,53,55-58} described strategies physicians use to cope with burnout. Table 2^{2,4,5,14,20,22,33,36,47,51,53,55-58} outlines the strategies postulated and reported by these studies as helpful in reducing burnout. Two studies^2,4 mentioned that physicians may turn to maladaptive behaviors, such as substance abuse, to cope with stress and burnout. Four studies^2,4,53,56 mentioned the importance of social support in fighting burnout and building resilience. Ten studies^{2,5,14,20,22,33,36,47,57,58} described the benefits of institutional interventions, such as what administrators can do to reduce the rate of burnout. Three studies^5,36,53 postulated different adaptive behaviors physicians can implement to reduce burnout.

Take-home points 

Research that focused on work/life balance and burnout found excessive time commitment to work is a major factor associated with poor work/life balance. Residents who worked >80 hours a week had a significantly higher burnout rate.⁵⁶ One study found that 70% of residents reported not getting enough sleep, 30% reported not having enough energy for relationships, and 39% reported that they were not eating or exercising due to time constraints.⁴ A high correlation was found between the number of hours worked per week and rates of burnout, emotional exhaustion, and depersonalization. Emotional exhaustion and depersonalization are aspects of burnout measured by the Maslach Burnout Inventory (MBI).²⁴ The excessive time commitment to work not only contributes to burnout but also prevents physicians from getting professional help. In 1 study, both residents (56%) and attendings (24%) reported that 1 of the biggest barriers to getting help for their burnout symptoms was the inability to take time off.³⁴ Research indicates that the hours worked per week and work/home conflicts were independently associated with burnout and career satisfaction.¹⁵ A decrease of weekly work hours may give physicians time to meet their responsibilities at work and home, allowing for a decrease in burnout and an increase in career satisfaction.

Increased work hours have also been found to be correlated with medical errors. One study found that those who worked 60 hours per week were significantly less likely to report any major medical errors in the previous 3 months compared with those who worked 80 hours per week.⁹ The risk for the number of medical errors has been reported as being 2-fold if surgeons are unable to combat the burnout.⁴⁹ On the other hand, a positive and supportive environment with easy access to resources to combat burnout and burnout prevention programs can reduce the frequency of medical errors, which also can reduce the risk of malpractice, thus further reducing stress and burnout.⁴³

Continue to: In response to resident complaints...

In response to resident complaints about long duty hours, a new rule has been implemented that states residents cannot work >16 hours per shift.³⁰ This rule has been found to increase quality of life and prevent burnout.³⁰

The amount of time spent on electronic medical records and documentation has been a major complaint from doctors and was identified as a factor contributing to burnout.⁴⁵ It can act as a time drain that impedes the physician from providing optimal patient care and cause additional stress. This suggests the need for organizations to find solutions to minimize this strain.

A concerning issue reported as an institutional factor and associated with burnout is mistreatment through discrimination, harassment, and physical or verbal abuse. A recent study found 45% of general and vascular surgeons reported being mistreated in some fashion.⁵⁷ The strategies reported as helpful for institutions to combat mistreatment include resilience training, improved mentorship, and implicit bias training.⁵⁷

Burnout has been positively correlated with anxiety and depression.⁶ A recent study reported that 13% of orthopedic surgery residents screened positive for depression.⁴⁴ Higher levels of burnout and depersonalization have been found to be closely associated with increased rates of suicidal ideation.¹⁷ In a study of vascular surgeons, 8% were found to report suicidal ideation, and this increased to 15% among vascular surgeons who had higher levels of depersonalization and emotional exhaustion,⁵⁸ both of which are associated with burnout. In another study, surgery residents and fellows were found to have lower levels of personal achievement and higher levels of depersonalization, depressive symptoms, alcohol abuse, and suicidal ideation compared to attending physicians and the general population.⁵⁴ These findings spell out the association between burnout and depressive symptoms among surgeons and emphasize the need for institutions to create a culture that supports the mental health needs of their physicians. Without access to supportive resources, residents resort to alternative methods that may be detrimental in the long run. In a recent study, 17% of residents admitted to using alcohol, including binge drinking, to cope with their stress.⁴

Burnout and depression are linked to physical health risks such as cardiovascular disease, diabetes, substance abuse, and male infertility.⁶ Exercise has been shown to be beneficial for stress reduction, which can lead to changes in metabolism, inflammation, coagulation, and autonomic function.⁶ One study of surgeons found aerobic exercise and strength training were associated with lower rates of burnout and a higher quality of life.⁵⁹

Continue to: The amount of burnout physicians...

The amount of burnout physicians experience can be determined by how they respond to adversities. Adaptive behaviors such as socializing, mindfulness, volunteering, and exercising have been found to be protective against burnout.^6,37,54 Resilience training and maintaining low stress at work can decrease burnout.³⁷ These findings highlight the need for physicians to be trained in the appropriate ways to combat their burnout symptoms.

Unfortunately, seeking help by health care professionals to improve mental health has been stigmatized, causing physicians to not seek help and instead resort to other ways to cope with their distress.^26,34 While some of these coping methods may be positive, others—such as substance abuse or stress eating—can be maladaptive, leading to a poor quality of life, and in some cases, suicide.⁵⁴ It is vital that effective mental health services become more accessible and for health care professionals to become aware of their maladaptive behaviors.³⁴

Institutions finding ways to ease the path for their physicians to seek professional help to combat burnout may mitigate its negative impact. One strategy is to embed access to mental health services within regular wellness checks. Institutions can use wellness checks to provide resources to physicians who need it. These interventions have been found to be effective because they give physicians a safe space to seek help and become aware of any factors that could lead to burnout.¹⁸ Apart from these direct attempts to combat burnout, program-sponsored social events would also promote social connectedness with colleagues and contribute to a sense of well-being that could help decrease levels of burnout and depression.¹³ Mentorship has been shown to play a crucial role in decreasing burnout among residents. One study that examined the role of mentorship reported that 55% of residents felt supported, and of these, 96% felt mentorship was critical to their success.¹⁸ The role of institutions in helping to improve the well-being of surgeons is highlighted by the finding that increasing workplace support results in psychological resilience that can mitigate burnout at its roots.²⁹

Bottom Line

Surgeons are at risk for burnout, which can impact their mental health and reduce their professional efficacy. Both institutions and surgeons themselves can take action to prevent burnout and treat burnout early when it occurs.

Related Resources

• Pahal P, Lippmann S. Building a better work/life balance. Current Psychiatry. 2021;20(8):e1-e2. doi:10.12788/cp.0158
• Gibson R, Hategan A. Physician burnout vs depression: recognize the signs. Current Psychiatry. 2019;18(10):41-42.

Burnout is an occupational phenomenon and a syndrome resulting from unsuccessfully managed chronic workplace stress. The characteristic features of burnout include feelings of exhaustion, cynicism, and reduced professional efficacy.¹ A career in surgery is associated with demanding and unpredictable work hours in a high-stress environment.^2-8 Research indicates that surgeons are at an elevated risk for developing burnout and mental health problems that can compromise patient care. A survey of the fellows of the American College of Surgeons found that 40% of surgeons experience burnout, 30% experience symptoms of depression, and 28% have a mental quality of life (QOL) score greater than one-half an SD below the population norm.^9,10 Surgeon burnout was also found to compromise the delivery of medical care.^9,10

To prevent serious harm to surgeons and patients, it is critical to understand the causative factors of burnout among surgeons and how they can be addressed. We conducted this systematic review to identify factors linked to burnout across surgical specialties and to suggest ways to mitigate these risk factors.  

Methods

To identify studies of burnout among surgeons, we conducted an electronic search of Ovid MEDLINE, Ovid PsycInfo, SCOPUS, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials. The headings and keywords used are listed in Supplemental Table 1. Studies met the inclusion criteria if they evaluated residents or attendings, used a tool to measure burnout, and examined any surgical specialty. Studies were excluded if they were published before 2010; were conducted outside the United States; were review articles, commentaries, or abstracts without full text articles; evaluated medical school students; were published in a language other than English; did not use a tool to measure burnout; or examined a nonsurgical specialty.  Our analysis was guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)¹¹ and is outlined in the Supplemental Figure.

Results

Surgical specialties and burnout

We identified 56 studies^2-10,12-58 that focused on specific surgical specialties in relation to burnout. Supplemental Table 2^2-10,12-58 lists these studies and the surgical specialties they evaluated.

Work/life balance factors

Fifteen studies^{2-5,14,15,18,19,22,32,34,38,39,47,57} examined the role of work/life balance in burnout. Table 1^{2-5,14,15,18,19,22,32,34,38,39,47,57} lists the work/life factors these studies identified as being linked to burnout. Six studies^{2,4,18,22,32,47} discussed how decreased leisure time was linked to burnout. Eleven studies^{2,4,14,15,19,22,34,38,39,42,57} associated inabilities to meet family commitments with burnout. A lack of time to spend with family and not having adequate time to raise children was more prevalent among women. Seven studies^{2,3,18,22,32,34,47} implicated increased time commitment to work as playing a role in burnout. This increased time commitment was also found to be a compounding variable for other factors, such as limited time for family and leisure.

Work hours

Fifteen studies^{2,7,14,20,21,30,34,41,42,44-46,50,52,56} examined work hours and burnout. Of these, 14^{2,7,14,20,21,30,34,42,44-46,50,52,56} found a correlation between increased work hours and burnout, while only 1 study⁴¹ found no correlation between these factors. 

Medical errors

Six studies^{2,14,18,43,49,52} discussed the role of burnout in medical errors. Of these, 5^{2,14,43,49,52} reported a correlation between burnout and medical errors, while 1 study¹⁸ found no link between burnout and medical errors. The medical errors were self-reported.^14,49 They included actions that resulted in patient harm, sample collection error, and errors in medication orders and laboratory test orders.²

Continue to: Institutional and organizational factors

Eighteen studies^{3,13,14,18,20,22,23,29,30,36-38,44,45,47,54,56,57} examined how different organizational factors play a role in burnout. Four studies^3,13,20,37 discussed administrative/bureaucratic work, 4^20,45,54,57 mentioned electronic medical documentation, 2^22,30 covered duty hour regulations, 3^18,45,57 discussed mistreatment of physicians, and 6^{13,18,23,44,47,56} described the importance of workplace support in addressing burnout.

Physical and mental health factors

Eighteen studies^{6,7,14,15,17,20,26,27,29,34,43,44,48,52,54,57-59} discussed aspects of physical and mental health linked to burnout. Among these, 3^34,43,59 discussed the importance of physical health and focused on how improving physical health can reduce stress and burnout. Three studies^6,17,58 noted the prevalence of suicidal ideation in both residents and attendings experiencing prolonged burnout. Five studies^{26,29,43,44,48} described the systematic barriers that inhibit physicians from getting professional help. Two studies^7,27 reported marital status as a factor for burnout; participants who were single reported higher levels of depression and suicidal ideation. Five studies^{6,14,15,54,57} outlined how depression is associated with burnout.

Strategies to mitigate burnout

Fifteen studies^{2,4,5,14,20,22,33,36,47,51,53,55-58} described strategies physicians use to cope with burnout. Table 2^{2,4,5,14,20,22,33,36,47,51,53,55-58} outlines the strategies postulated and reported by these studies as helpful in reducing burnout. Two studies^2,4 mentioned that physicians may turn to maladaptive behaviors, such as substance abuse, to cope with stress and burnout. Four studies^2,4,53,56 mentioned the importance of social support in fighting burnout and building resilience. Ten studies^{2,5,14,20,22,33,36,47,57,58} described the benefits of institutional interventions, such as what administrators can do to reduce the rate of burnout. Three studies^5,36,53 postulated different adaptive behaviors physicians can implement to reduce burnout.

Take-home points 

Research that focused on work/life balance and burnout found excessive time commitment to work is a major factor associated with poor work/life balance. Residents who worked >80 hours a week had a significantly higher burnout rate.⁵⁶ One study found that 70% of residents reported not getting enough sleep, 30% reported not having enough energy for relationships, and 39% reported that they were not eating or exercising due to time constraints.⁴ A high correlation was found between the number of hours worked per week and rates of burnout, emotional exhaustion, and depersonalization. Emotional exhaustion and depersonalization are aspects of burnout measured by the Maslach Burnout Inventory (MBI).²⁴ The excessive time commitment to work not only contributes to burnout but also prevents physicians from getting professional help. In 1 study, both residents (56%) and attendings (24%) reported that 1 of the biggest barriers to getting help for their burnout symptoms was the inability to take time off.³⁴ Research indicates that the hours worked per week and work/home conflicts were independently associated with burnout and career satisfaction.¹⁵ A decrease of weekly work hours may give physicians time to meet their responsibilities at work and home, allowing for a decrease in burnout and an increase in career satisfaction.

Increased work hours have also been found to be correlated with medical errors. One study found that those who worked 60 hours per week were significantly less likely to report any major medical errors in the previous 3 months compared with those who worked 80 hours per week.⁹ The risk for the number of medical errors has been reported as being 2-fold if surgeons are unable to combat the burnout.⁴⁹ On the other hand, a positive and supportive environment with easy access to resources to combat burnout and burnout prevention programs can reduce the frequency of medical errors, which also can reduce the risk of malpractice, thus further reducing stress and burnout.⁴³

Continue to: In response to resident complaints...

In response to resident complaints about long duty hours, a new rule has been implemented that states residents cannot work >16 hours per shift.³⁰ This rule has been found to increase quality of life and prevent burnout.³⁰

The amount of time spent on electronic medical records and documentation has been a major complaint from doctors and was identified as a factor contributing to burnout.⁴⁵ It can act as a time drain that impedes the physician from providing optimal patient care and cause additional stress. This suggests the need for organizations to find solutions to minimize this strain.

A concerning issue reported as an institutional factor and associated with burnout is mistreatment through discrimination, harassment, and physical or verbal abuse. A recent study found 45% of general and vascular surgeons reported being mistreated in some fashion.⁵⁷ The strategies reported as helpful for institutions to combat mistreatment include resilience training, improved mentorship, and implicit bias training.⁵⁷

Burnout has been positively correlated with anxiety and depression.⁶ A recent study reported that 13% of orthopedic surgery residents screened positive for depression.⁴⁴ Higher levels of burnout and depersonalization have been found to be closely associated with increased rates of suicidal ideation.¹⁷ In a study of vascular surgeons, 8% were found to report suicidal ideation, and this increased to 15% among vascular surgeons who had higher levels of depersonalization and emotional exhaustion,⁵⁸ both of which are associated with burnout. In another study, surgery residents and fellows were found to have lower levels of personal achievement and higher levels of depersonalization, depressive symptoms, alcohol abuse, and suicidal ideation compared to attending physicians and the general population.⁵⁴ These findings spell out the association between burnout and depressive symptoms among surgeons and emphasize the need for institutions to create a culture that supports the mental health needs of their physicians. Without access to supportive resources, residents resort to alternative methods that may be detrimental in the long run. In a recent study, 17% of residents admitted to using alcohol, including binge drinking, to cope with their stress.⁴

Burnout and depression are linked to physical health risks such as cardiovascular disease, diabetes, substance abuse, and male infertility.⁶ Exercise has been shown to be beneficial for stress reduction, which can lead to changes in metabolism, inflammation, coagulation, and autonomic function.⁶ One study of surgeons found aerobic exercise and strength training were associated with lower rates of burnout and a higher quality of life.⁵⁹

Continue to: The amount of burnout physicians...

The amount of burnout physicians experience can be determined by how they respond to adversities. Adaptive behaviors such as socializing, mindfulness, volunteering, and exercising have been found to be protective against burnout.^6,37,54 Resilience training and maintaining low stress at work can decrease burnout.³⁷ These findings highlight the need for physicians to be trained in the appropriate ways to combat their burnout symptoms.

Unfortunately, seeking help by health care professionals to improve mental health has been stigmatized, causing physicians to not seek help and instead resort to other ways to cope with their distress.^26,34 While some of these coping methods may be positive, others—such as substance abuse or stress eating—can be maladaptive, leading to a poor quality of life, and in some cases, suicide.⁵⁴ It is vital that effective mental health services become more accessible and for health care professionals to become aware of their maladaptive behaviors.³⁴

Institutions finding ways to ease the path for their physicians to seek professional help to combat burnout may mitigate its negative impact. One strategy is to embed access to mental health services within regular wellness checks. Institutions can use wellness checks to provide resources to physicians who need it. These interventions have been found to be effective because they give physicians a safe space to seek help and become aware of any factors that could lead to burnout.¹⁸ Apart from these direct attempts to combat burnout, program-sponsored social events would also promote social connectedness with colleagues and contribute to a sense of well-being that could help decrease levels of burnout and depression.¹³ Mentorship has been shown to play a crucial role in decreasing burnout among residents. One study that examined the role of mentorship reported that 55% of residents felt supported, and of these, 96% felt mentorship was critical to their success.¹⁸ The role of institutions in helping to improve the well-being of surgeons is highlighted by the finding that increasing workplace support results in psychological resilience that can mitigate burnout at its roots.²⁹

Bottom Line

Surgeons are at risk for burnout, which can impact their mental health and reduce their professional efficacy. Both institutions and surgeons themselves can take action to prevent burnout and treat burnout early when it occurs.

Related Resources

• Pahal P, Lippmann S. Building a better work/life balance. Current Psychiatry. 2021;20(8):e1-e2. doi:10.12788/cp.0158
• Gibson R, Hategan A. Physician burnout vs depression: recognize the signs. Current Psychiatry. 2019;18(10):41-42.