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Is it time to stop treating high triglycerides?
The publication of the PROMINENT trial, where pemafibrate successfully lowered high levels but was not associated with a lower risk for cardiovascular events, reinforced the point. Is it time to stop measuring and treating high triglycerides?
There may be noncardiovascular reasons to treat hypertriglyceridemia. Pancreatitis is the most cited one, given that the risk for pancreatitis increases with increasing triglyceride levels, especially in patients with a prior episode.
There may also be practical reasons to lower trigs. Because most cholesterol panels use the Friedewald equation to calculate low-density lipoprotein cholesterol (LDL-C) rather than measuring it directly, very high triglyceride levels can invalidate the calculation and return error messages on lab reports.
But we now have alternatives to measuring LDL-C, including non–high-density lipoprotein cholesterol (HDL-C) and apolipoprotein B (apoB), that better predict risk and are usable even in the setting of nonfasting samples when triglycerides are elevated.
Independent cardiovascular risk factor?
If we are going to measure and treat high triglycerides for cardiovascular reasons, the relevant question is, are high triglycerides an independent risk factor for cardiovascular disease?
Proponents have a broad swath of supportive literature to point at. Multiple studies have shown an association between triglyceride levels and cardiovascular risk. The evidence even extends beyond traditional epidemiologic analyses, to genetic studies that should be free from some of the problems seen in observational cohorts.
But it is difficult to be certain whether these associations are causal or merely confounding. An unhealthy diet will increase triglycerides, as will alcohol. Patients with diabetes or metabolic syndrome have high triglycerides. So do patients with nephrotic syndrome or hypothyroidism, or hypertensive patients taking thiazide diuretics. Adjusting for these baseline factors is possible but imperfect, and residual confounding is always an issue. An analysis of the Reykjavik and the EPIC-Norfolk studies found an association between triglyceride levels and cardiovascular risk. That risk was attenuated, but not eliminated, when adjusted for traditional risk factors such as age, smoking, blood pressure, diabetes, and cholesterol.
Randomized trials of triglyceride-lowering therapies would help resolve the question of whether hypertriglyceridemia contributes to coronary disease or simply identifies high-risk patients. Early trials seemed to support the idea of a causal link. The Helsinki Heart Study randomized patients to gemfibrozil or placebo and found a 34% relative risk reduction in coronary artery disease with the fibrate. But gemfibrozil didn’t only reduce triglycerides. It also increased HDL-C and lowered LDL-C relative to placebo, which may explain the observed benefit.
Gemfibrozil is rarely used today because we can achieve much greater LDL-C reductions with statins, as well as ezetimibe and PCSK9 inhibitors. The success of these drugs may not leave any room for triglyceride-lowering medications.
The pre- vs. post-statin era
In the 2005 FIELD study, participants were randomized to receive fenofibrate or placebo. Although patients weren’t taking statin at study entry, 17% of the placebo group started taking one during the trial. Fenofibrate wasn’t associated with a reduction in the primary endpoint, a combination of coronary heart disease death or nonfatal myocardial infarction (MI). Among the many secondary endpoints, nonfatal MI was lower but cardiovascular mortality was not in the fibrate-treated patients. In the same vein, the 2010 ACCORD study randomized patients to receive simvastatin plus fenofibrate or simvastatin alone. The composite primary outcome of MI, stroke, and cardiovascular mortality was not lowered nor were any secondary outcomes with the combination therapy. In the statin era, triglyceride-lowering therapies have not shown much benefit.
The final nail in the coffin may very well be the aforementioned PROMINENT trial. The new agent, pemafibrate, fared no better than its predecessor fenofibrate. Pemafibrate had no impact on the study’s primary composite outcome of nonfatal MI, stroke, coronary revascularization, or cardiovascular death despite being very effective at lowering triglycerides (by more than 25%). Patients treated with pemafibrate had increased LDL-C and apoB compared with the placebo group. When you realize that, the results of the study are not very surprising.
Some point to the results of REDUCE-IT as proof that triglycerides are still a valid target for pharmacotherapy. The debate on whether REDUCE-IT tested a good drug or a bad placebo is one for another day. The salient point for today is that the benefits of eicosapentaenoic acid (EPA) were seen regardless of either baseline or final triglyceride level. EPA may lower cardiac risk, but there is no widespread consensus that it does so by lowering triglycerides. There may be other mechanisms at work.
You could still argue that high triglycerides have value as a risk prediction tool even if their role as a target for drug therapy is questionable. There was a time when medications to lower triglycerides had a benefit. But this is the post-statin era, and that time has passed.
If you see patients with high triglycerides, treating them with triglyceride-lowering medication probably isn’t going to reduce their cardiovascular risk. Dietary interventions, encouraging exercise, and reducing alcohol consumption are better options. Not only will they lead to lower cholesterol levels, but they’ll lower cardiovascular risk, too.
Dr. Labos is a cardiologist at Hôpital Notre-Dame, Montreal, with a degree in epidemiology. He has disclosed no relevant financial relationships. He spends most of his time doing things that he doesn’t get paid for, like research, teaching, and podcasting. Occasionally he finds time to practice cardiology to pay the rent. He realizes that half of his research findings will be disproved in 5 years; he just doesn’t know which half. He is a regular contributor to the Montreal Gazette, CJAD radio, and CTV television in Montreal and is host of the award-winning podcast The Body of Evidence. The Body of Evidence.
A version of this article originally appeared on Medscape.com.
The publication of the PROMINENT trial, where pemafibrate successfully lowered high levels but was not associated with a lower risk for cardiovascular events, reinforced the point. Is it time to stop measuring and treating high triglycerides?
There may be noncardiovascular reasons to treat hypertriglyceridemia. Pancreatitis is the most cited one, given that the risk for pancreatitis increases with increasing triglyceride levels, especially in patients with a prior episode.
There may also be practical reasons to lower trigs. Because most cholesterol panels use the Friedewald equation to calculate low-density lipoprotein cholesterol (LDL-C) rather than measuring it directly, very high triglyceride levels can invalidate the calculation and return error messages on lab reports.
But we now have alternatives to measuring LDL-C, including non–high-density lipoprotein cholesterol (HDL-C) and apolipoprotein B (apoB), that better predict risk and are usable even in the setting of nonfasting samples when triglycerides are elevated.
Independent cardiovascular risk factor?
If we are going to measure and treat high triglycerides for cardiovascular reasons, the relevant question is, are high triglycerides an independent risk factor for cardiovascular disease?
Proponents have a broad swath of supportive literature to point at. Multiple studies have shown an association between triglyceride levels and cardiovascular risk. The evidence even extends beyond traditional epidemiologic analyses, to genetic studies that should be free from some of the problems seen in observational cohorts.
But it is difficult to be certain whether these associations are causal or merely confounding. An unhealthy diet will increase triglycerides, as will alcohol. Patients with diabetes or metabolic syndrome have high triglycerides. So do patients with nephrotic syndrome or hypothyroidism, or hypertensive patients taking thiazide diuretics. Adjusting for these baseline factors is possible but imperfect, and residual confounding is always an issue. An analysis of the Reykjavik and the EPIC-Norfolk studies found an association between triglyceride levels and cardiovascular risk. That risk was attenuated, but not eliminated, when adjusted for traditional risk factors such as age, smoking, blood pressure, diabetes, and cholesterol.
Randomized trials of triglyceride-lowering therapies would help resolve the question of whether hypertriglyceridemia contributes to coronary disease or simply identifies high-risk patients. Early trials seemed to support the idea of a causal link. The Helsinki Heart Study randomized patients to gemfibrozil or placebo and found a 34% relative risk reduction in coronary artery disease with the fibrate. But gemfibrozil didn’t only reduce triglycerides. It also increased HDL-C and lowered LDL-C relative to placebo, which may explain the observed benefit.
Gemfibrozil is rarely used today because we can achieve much greater LDL-C reductions with statins, as well as ezetimibe and PCSK9 inhibitors. The success of these drugs may not leave any room for triglyceride-lowering medications.
The pre- vs. post-statin era
In the 2005 FIELD study, participants were randomized to receive fenofibrate or placebo. Although patients weren’t taking statin at study entry, 17% of the placebo group started taking one during the trial. Fenofibrate wasn’t associated with a reduction in the primary endpoint, a combination of coronary heart disease death or nonfatal myocardial infarction (MI). Among the many secondary endpoints, nonfatal MI was lower but cardiovascular mortality was not in the fibrate-treated patients. In the same vein, the 2010 ACCORD study randomized patients to receive simvastatin plus fenofibrate or simvastatin alone. The composite primary outcome of MI, stroke, and cardiovascular mortality was not lowered nor were any secondary outcomes with the combination therapy. In the statin era, triglyceride-lowering therapies have not shown much benefit.
The final nail in the coffin may very well be the aforementioned PROMINENT trial. The new agent, pemafibrate, fared no better than its predecessor fenofibrate. Pemafibrate had no impact on the study’s primary composite outcome of nonfatal MI, stroke, coronary revascularization, or cardiovascular death despite being very effective at lowering triglycerides (by more than 25%). Patients treated with pemafibrate had increased LDL-C and apoB compared with the placebo group. When you realize that, the results of the study are not very surprising.
Some point to the results of REDUCE-IT as proof that triglycerides are still a valid target for pharmacotherapy. The debate on whether REDUCE-IT tested a good drug or a bad placebo is one for another day. The salient point for today is that the benefits of eicosapentaenoic acid (EPA) were seen regardless of either baseline or final triglyceride level. EPA may lower cardiac risk, but there is no widespread consensus that it does so by lowering triglycerides. There may be other mechanisms at work.
You could still argue that high triglycerides have value as a risk prediction tool even if their role as a target for drug therapy is questionable. There was a time when medications to lower triglycerides had a benefit. But this is the post-statin era, and that time has passed.
If you see patients with high triglycerides, treating them with triglyceride-lowering medication probably isn’t going to reduce their cardiovascular risk. Dietary interventions, encouraging exercise, and reducing alcohol consumption are better options. Not only will they lead to lower cholesterol levels, but they’ll lower cardiovascular risk, too.
Dr. Labos is a cardiologist at Hôpital Notre-Dame, Montreal, with a degree in epidemiology. He has disclosed no relevant financial relationships. He spends most of his time doing things that he doesn’t get paid for, like research, teaching, and podcasting. Occasionally he finds time to practice cardiology to pay the rent. He realizes that half of his research findings will be disproved in 5 years; he just doesn’t know which half. He is a regular contributor to the Montreal Gazette, CJAD radio, and CTV television in Montreal and is host of the award-winning podcast The Body of Evidence. The Body of Evidence.
A version of this article originally appeared on Medscape.com.
The publication of the PROMINENT trial, where pemafibrate successfully lowered high levels but was not associated with a lower risk for cardiovascular events, reinforced the point. Is it time to stop measuring and treating high triglycerides?
There may be noncardiovascular reasons to treat hypertriglyceridemia. Pancreatitis is the most cited one, given that the risk for pancreatitis increases with increasing triglyceride levels, especially in patients with a prior episode.
There may also be practical reasons to lower trigs. Because most cholesterol panels use the Friedewald equation to calculate low-density lipoprotein cholesterol (LDL-C) rather than measuring it directly, very high triglyceride levels can invalidate the calculation and return error messages on lab reports.
But we now have alternatives to measuring LDL-C, including non–high-density lipoprotein cholesterol (HDL-C) and apolipoprotein B (apoB), that better predict risk and are usable even in the setting of nonfasting samples when triglycerides are elevated.
Independent cardiovascular risk factor?
If we are going to measure and treat high triglycerides for cardiovascular reasons, the relevant question is, are high triglycerides an independent risk factor for cardiovascular disease?
Proponents have a broad swath of supportive literature to point at. Multiple studies have shown an association between triglyceride levels and cardiovascular risk. The evidence even extends beyond traditional epidemiologic analyses, to genetic studies that should be free from some of the problems seen in observational cohorts.
But it is difficult to be certain whether these associations are causal or merely confounding. An unhealthy diet will increase triglycerides, as will alcohol. Patients with diabetes or metabolic syndrome have high triglycerides. So do patients with nephrotic syndrome or hypothyroidism, or hypertensive patients taking thiazide diuretics. Adjusting for these baseline factors is possible but imperfect, and residual confounding is always an issue. An analysis of the Reykjavik and the EPIC-Norfolk studies found an association between triglyceride levels and cardiovascular risk. That risk was attenuated, but not eliminated, when adjusted for traditional risk factors such as age, smoking, blood pressure, diabetes, and cholesterol.
Randomized trials of triglyceride-lowering therapies would help resolve the question of whether hypertriglyceridemia contributes to coronary disease or simply identifies high-risk patients. Early trials seemed to support the idea of a causal link. The Helsinki Heart Study randomized patients to gemfibrozil or placebo and found a 34% relative risk reduction in coronary artery disease with the fibrate. But gemfibrozil didn’t only reduce triglycerides. It also increased HDL-C and lowered LDL-C relative to placebo, which may explain the observed benefit.
Gemfibrozil is rarely used today because we can achieve much greater LDL-C reductions with statins, as well as ezetimibe and PCSK9 inhibitors. The success of these drugs may not leave any room for triglyceride-lowering medications.
The pre- vs. post-statin era
In the 2005 FIELD study, participants were randomized to receive fenofibrate or placebo. Although patients weren’t taking statin at study entry, 17% of the placebo group started taking one during the trial. Fenofibrate wasn’t associated with a reduction in the primary endpoint, a combination of coronary heart disease death or nonfatal myocardial infarction (MI). Among the many secondary endpoints, nonfatal MI was lower but cardiovascular mortality was not in the fibrate-treated patients. In the same vein, the 2010 ACCORD study randomized patients to receive simvastatin plus fenofibrate or simvastatin alone. The composite primary outcome of MI, stroke, and cardiovascular mortality was not lowered nor were any secondary outcomes with the combination therapy. In the statin era, triglyceride-lowering therapies have not shown much benefit.
The final nail in the coffin may very well be the aforementioned PROMINENT trial. The new agent, pemafibrate, fared no better than its predecessor fenofibrate. Pemafibrate had no impact on the study’s primary composite outcome of nonfatal MI, stroke, coronary revascularization, or cardiovascular death despite being very effective at lowering triglycerides (by more than 25%). Patients treated with pemafibrate had increased LDL-C and apoB compared with the placebo group. When you realize that, the results of the study are not very surprising.
Some point to the results of REDUCE-IT as proof that triglycerides are still a valid target for pharmacotherapy. The debate on whether REDUCE-IT tested a good drug or a bad placebo is one for another day. The salient point for today is that the benefits of eicosapentaenoic acid (EPA) were seen regardless of either baseline or final triglyceride level. EPA may lower cardiac risk, but there is no widespread consensus that it does so by lowering triglycerides. There may be other mechanisms at work.
You could still argue that high triglycerides have value as a risk prediction tool even if their role as a target for drug therapy is questionable. There was a time when medications to lower triglycerides had a benefit. But this is the post-statin era, and that time has passed.
If you see patients with high triglycerides, treating them with triglyceride-lowering medication probably isn’t going to reduce their cardiovascular risk. Dietary interventions, encouraging exercise, and reducing alcohol consumption are better options. Not only will they lead to lower cholesterol levels, but they’ll lower cardiovascular risk, too.
Dr. Labos is a cardiologist at Hôpital Notre-Dame, Montreal, with a degree in epidemiology. He has disclosed no relevant financial relationships. He spends most of his time doing things that he doesn’t get paid for, like research, teaching, and podcasting. Occasionally he finds time to practice cardiology to pay the rent. He realizes that half of his research findings will be disproved in 5 years; he just doesn’t know which half. He is a regular contributor to the Montreal Gazette, CJAD radio, and CTV television in Montreal and is host of the award-winning podcast The Body of Evidence. The Body of Evidence.
A version of this article originally appeared on Medscape.com.
Stutz: The psychiatrist as movie star
For as long as I can remember, psychiatrists have talked about what the appropriate boundaries are for self-disclosure about personal issues with patients. There is obviously no exact answer as to what is acceptable to disclose; this depends on the doctor, the patient, the “brand” of psychotherapy, the patient’s issues, the nature of what is being disclosed, and maybe the alignment of the stars on that particular day. “Stutz,” the Netflix documentary that Oscar-nominated actor/director Jonah Hill has made about his psychiatrist, Phil Stutz, MD, adds a whole new chapter to the discussion.
“Okay, entertain me,” Dr. Stutz says as his patient takes a seat. The therapeutic relationship and the paradigm Dr. Stutz has created to help his patients has been healing for Jonah Hill. The very serious and intimate dialogue that follows unfolds with moments of humor, warmth, and open affection. Hill candidly tells us why he is making this documentary – to share what he has learned and to honor his therapist – but we don’t know why Dr. Stutz has agreed to the endeavor and we’re left to our own inferences.
Dr. Stutz is the coauthor, with Barry Michels, of a best-selling self-help book, “The Tools: 5 Tools to Help You Find Courage, Creativity, and Willpower – and Inspire You to Live Life in Forward Motion.” He talks about his restlessness with the psychodynamic method during his training as a resident in New York – he wanted to offer his patients more immediate relief and a supervisor told him, “Don’t you dare!”
In the film, he talks about giving patients hope and direction. And Hill makes the comment, “In traditional therapy, you’re paying this person and you save all your problems for them, and they just listen, and your friends – who are idiots – give you advice, unsolicited, and you want your friends just to listen, and you want your therapist to give you advice!” Dr. Stutz gives advice and he is like no other therapist Jonah has ever had.
The premise of the film is that we are watching a single therapy session and Dr. Stutz will discuss the use of his tools and techniques that Hill has found helpful. Jonah is the interviewer, and when the doctor suggests it would be helpful if Jonah talked about his life, the patient/director rebuffs him; this documentary is about the psychiatrist.
Early in the film an alarm goes off, Dr. Stutz does not hear it, and Jonah has to remind him that it’s time for him to take his pills. The psychiatrist has Parkinson’s disease and how it has affected him becomes one focal point for the film. We later learn that he lost a younger brother as a child (something Hill did not know before they started filming) and grew up in the shadow of that loss. His extroverted father made it clear that medicine was the only acceptable career path for his son, and his introverted and depressed mother spent her days proclaiming that all men were as awful as her own abusive father.
About a third of the way through the film, the focus shifts. Jonah suddenly confesses that he is feeling stuck with regard to the movie, that he is troubled by the fact that he has not been able to share his distress with Dr. Stutz during their real-life, unfilmed therapy sessions, and the viewers learn that the single-session concept was disingenuous – they have been filming this documentary for two years, against a green screen and not in an office, always wearing the same clothes, and Jonah pulls off a wig that he wears to disguise the fact that he changed his hairstyle months earlier.
It’s a bit unnerving as they throw the wig around, and Jonah agrees to be more open about the issues he has struggled with. He acknowledges that this has been difficult, and he says, “I just keep asking myself, like, was this a f***ing horrible idea for a patient to make a movie about his therapist?” From my perspective as a psychiatrist-viewer, it’s a good question to ask!
Dr. Stutz reassures Jonah that it is okay to be vulnerable. “Failure, weakness, vulnerability – it’s like a connector, it connects you to the rest of the world.” A super-sized cardboard cutout of an obese 14-year-old Jonah now joins the room, and we learn that he continues to struggle with his self-image. Things get more real.
Peppered throughout the film, there are lessons from Dr. Stutz about his “tools,” constructs he uses to help people restructure their worlds and take action to move forward. One such construct he calls “the maze,” which occurs when one person in an interpersonal relationship is waiting for fairness and becomes preoccupied with feeling injured.
Jonah inquires about Dr. Stutz’s romantic life and the therapist replies with a transparency that overrides our usual professional boundaries. We all learn that Dr. Stutz is not in a relationship, he’s never been married, but there is a woman he has had some involvement with on and off for 40 years. Jonah’s line of questioning rivals that of any therapist. “How do you think it affects you, having your mom hate men and you being a man?” Dr. Stutz admits that he can never feel safe with women. “Did you ever override that wall you built with your mom and get close to a woman?” When Jonah professes, “I don’t feel anything but love for you and I just want you to be happy,” my own feeling was that the tables had turned too far, that the therapist’s failed romantic life risked being a burden to the patient.
Still, there is something about the relationship between the two men that is touching and beautiful. Dr. Stutz as a therapist is charismatic, caring, self-assured, and optimistic, and he radiates hope and certainty. He mixes an intense intimacy with humor in a way that is both authentic and entertaining. The interspersed jokes break the intensity, but they don’t diminish his wisdom and the healing he imparts.
Dr. Stutz is a psychiatrist, and his strength is clearly as a psychotherapist, yet there is not a single mention of psychotropic medications – there is a banter about recreational drugs and medications for Parkinson’s disease. If Hill is taking medication for depression or anxiety, and if prescribing is part of Dr. Stutz’s arsenal, the viewer is not made aware of this.
Dr. Stutz eschews the slow, detached, and “neutral” pace of psychodynamic therapy and the whole concept of the therapist as a blank wall for the transference to play out on, but here the transference screams: Jonah loves him, he respect and honors him, he wants him to be happy, and he is afraid of losing him.
“Stutz” is a movie about a larger-than-life psychiatrist, one whose warmth and inspiration are healing. I imagine his tools are helpful, but his personality is what carries the load. If a viewer has not had experience with psychiatry, and this film inspires him to begin therapy, there may be a good deal of disappointment. In this case, the patient is a successful actor, and one might wonder if that, together with the entire years-long project of filming, has altered the relationship well beyond the usual therapeutic hour.
Dr. Miller is a coauthor of “Committed: The Battle Over Involuntary Psychiatric Care” (Baltimore: Johns Hopkins University Press, 2016). She has a private practice and is an assistant professor of psychiatry and behavioral sciences at Johns Hopkins University in Baltimore.
For as long as I can remember, psychiatrists have talked about what the appropriate boundaries are for self-disclosure about personal issues with patients. There is obviously no exact answer as to what is acceptable to disclose; this depends on the doctor, the patient, the “brand” of psychotherapy, the patient’s issues, the nature of what is being disclosed, and maybe the alignment of the stars on that particular day. “Stutz,” the Netflix documentary that Oscar-nominated actor/director Jonah Hill has made about his psychiatrist, Phil Stutz, MD, adds a whole new chapter to the discussion.
“Okay, entertain me,” Dr. Stutz says as his patient takes a seat. The therapeutic relationship and the paradigm Dr. Stutz has created to help his patients has been healing for Jonah Hill. The very serious and intimate dialogue that follows unfolds with moments of humor, warmth, and open affection. Hill candidly tells us why he is making this documentary – to share what he has learned and to honor his therapist – but we don’t know why Dr. Stutz has agreed to the endeavor and we’re left to our own inferences.
Dr. Stutz is the coauthor, with Barry Michels, of a best-selling self-help book, “The Tools: 5 Tools to Help You Find Courage, Creativity, and Willpower – and Inspire You to Live Life in Forward Motion.” He talks about his restlessness with the psychodynamic method during his training as a resident in New York – he wanted to offer his patients more immediate relief and a supervisor told him, “Don’t you dare!”
In the film, he talks about giving patients hope and direction. And Hill makes the comment, “In traditional therapy, you’re paying this person and you save all your problems for them, and they just listen, and your friends – who are idiots – give you advice, unsolicited, and you want your friends just to listen, and you want your therapist to give you advice!” Dr. Stutz gives advice and he is like no other therapist Jonah has ever had.
The premise of the film is that we are watching a single therapy session and Dr. Stutz will discuss the use of his tools and techniques that Hill has found helpful. Jonah is the interviewer, and when the doctor suggests it would be helpful if Jonah talked about his life, the patient/director rebuffs him; this documentary is about the psychiatrist.
Early in the film an alarm goes off, Dr. Stutz does not hear it, and Jonah has to remind him that it’s time for him to take his pills. The psychiatrist has Parkinson’s disease and how it has affected him becomes one focal point for the film. We later learn that he lost a younger brother as a child (something Hill did not know before they started filming) and grew up in the shadow of that loss. His extroverted father made it clear that medicine was the only acceptable career path for his son, and his introverted and depressed mother spent her days proclaiming that all men were as awful as her own abusive father.
About a third of the way through the film, the focus shifts. Jonah suddenly confesses that he is feeling stuck with regard to the movie, that he is troubled by the fact that he has not been able to share his distress with Dr. Stutz during their real-life, unfilmed therapy sessions, and the viewers learn that the single-session concept was disingenuous – they have been filming this documentary for two years, against a green screen and not in an office, always wearing the same clothes, and Jonah pulls off a wig that he wears to disguise the fact that he changed his hairstyle months earlier.
It’s a bit unnerving as they throw the wig around, and Jonah agrees to be more open about the issues he has struggled with. He acknowledges that this has been difficult, and he says, “I just keep asking myself, like, was this a f***ing horrible idea for a patient to make a movie about his therapist?” From my perspective as a psychiatrist-viewer, it’s a good question to ask!
Dr. Stutz reassures Jonah that it is okay to be vulnerable. “Failure, weakness, vulnerability – it’s like a connector, it connects you to the rest of the world.” A super-sized cardboard cutout of an obese 14-year-old Jonah now joins the room, and we learn that he continues to struggle with his self-image. Things get more real.
Peppered throughout the film, there are lessons from Dr. Stutz about his “tools,” constructs he uses to help people restructure their worlds and take action to move forward. One such construct he calls “the maze,” which occurs when one person in an interpersonal relationship is waiting for fairness and becomes preoccupied with feeling injured.
Jonah inquires about Dr. Stutz’s romantic life and the therapist replies with a transparency that overrides our usual professional boundaries. We all learn that Dr. Stutz is not in a relationship, he’s never been married, but there is a woman he has had some involvement with on and off for 40 years. Jonah’s line of questioning rivals that of any therapist. “How do you think it affects you, having your mom hate men and you being a man?” Dr. Stutz admits that he can never feel safe with women. “Did you ever override that wall you built with your mom and get close to a woman?” When Jonah professes, “I don’t feel anything but love for you and I just want you to be happy,” my own feeling was that the tables had turned too far, that the therapist’s failed romantic life risked being a burden to the patient.
Still, there is something about the relationship between the two men that is touching and beautiful. Dr. Stutz as a therapist is charismatic, caring, self-assured, and optimistic, and he radiates hope and certainty. He mixes an intense intimacy with humor in a way that is both authentic and entertaining. The interspersed jokes break the intensity, but they don’t diminish his wisdom and the healing he imparts.
Dr. Stutz is a psychiatrist, and his strength is clearly as a psychotherapist, yet there is not a single mention of psychotropic medications – there is a banter about recreational drugs and medications for Parkinson’s disease. If Hill is taking medication for depression or anxiety, and if prescribing is part of Dr. Stutz’s arsenal, the viewer is not made aware of this.
Dr. Stutz eschews the slow, detached, and “neutral” pace of psychodynamic therapy and the whole concept of the therapist as a blank wall for the transference to play out on, but here the transference screams: Jonah loves him, he respect and honors him, he wants him to be happy, and he is afraid of losing him.
“Stutz” is a movie about a larger-than-life psychiatrist, one whose warmth and inspiration are healing. I imagine his tools are helpful, but his personality is what carries the load. If a viewer has not had experience with psychiatry, and this film inspires him to begin therapy, there may be a good deal of disappointment. In this case, the patient is a successful actor, and one might wonder if that, together with the entire years-long project of filming, has altered the relationship well beyond the usual therapeutic hour.
Dr. Miller is a coauthor of “Committed: The Battle Over Involuntary Psychiatric Care” (Baltimore: Johns Hopkins University Press, 2016). She has a private practice and is an assistant professor of psychiatry and behavioral sciences at Johns Hopkins University in Baltimore.
For as long as I can remember, psychiatrists have talked about what the appropriate boundaries are for self-disclosure about personal issues with patients. There is obviously no exact answer as to what is acceptable to disclose; this depends on the doctor, the patient, the “brand” of psychotherapy, the patient’s issues, the nature of what is being disclosed, and maybe the alignment of the stars on that particular day. “Stutz,” the Netflix documentary that Oscar-nominated actor/director Jonah Hill has made about his psychiatrist, Phil Stutz, MD, adds a whole new chapter to the discussion.
“Okay, entertain me,” Dr. Stutz says as his patient takes a seat. The therapeutic relationship and the paradigm Dr. Stutz has created to help his patients has been healing for Jonah Hill. The very serious and intimate dialogue that follows unfolds with moments of humor, warmth, and open affection. Hill candidly tells us why he is making this documentary – to share what he has learned and to honor his therapist – but we don’t know why Dr. Stutz has agreed to the endeavor and we’re left to our own inferences.
Dr. Stutz is the coauthor, with Barry Michels, of a best-selling self-help book, “The Tools: 5 Tools to Help You Find Courage, Creativity, and Willpower – and Inspire You to Live Life in Forward Motion.” He talks about his restlessness with the psychodynamic method during his training as a resident in New York – he wanted to offer his patients more immediate relief and a supervisor told him, “Don’t you dare!”
In the film, he talks about giving patients hope and direction. And Hill makes the comment, “In traditional therapy, you’re paying this person and you save all your problems for them, and they just listen, and your friends – who are idiots – give you advice, unsolicited, and you want your friends just to listen, and you want your therapist to give you advice!” Dr. Stutz gives advice and he is like no other therapist Jonah has ever had.
The premise of the film is that we are watching a single therapy session and Dr. Stutz will discuss the use of his tools and techniques that Hill has found helpful. Jonah is the interviewer, and when the doctor suggests it would be helpful if Jonah talked about his life, the patient/director rebuffs him; this documentary is about the psychiatrist.
Early in the film an alarm goes off, Dr. Stutz does not hear it, and Jonah has to remind him that it’s time for him to take his pills. The psychiatrist has Parkinson’s disease and how it has affected him becomes one focal point for the film. We later learn that he lost a younger brother as a child (something Hill did not know before they started filming) and grew up in the shadow of that loss. His extroverted father made it clear that medicine was the only acceptable career path for his son, and his introverted and depressed mother spent her days proclaiming that all men were as awful as her own abusive father.
About a third of the way through the film, the focus shifts. Jonah suddenly confesses that he is feeling stuck with regard to the movie, that he is troubled by the fact that he has not been able to share his distress with Dr. Stutz during their real-life, unfilmed therapy sessions, and the viewers learn that the single-session concept was disingenuous – they have been filming this documentary for two years, against a green screen and not in an office, always wearing the same clothes, and Jonah pulls off a wig that he wears to disguise the fact that he changed his hairstyle months earlier.
It’s a bit unnerving as they throw the wig around, and Jonah agrees to be more open about the issues he has struggled with. He acknowledges that this has been difficult, and he says, “I just keep asking myself, like, was this a f***ing horrible idea for a patient to make a movie about his therapist?” From my perspective as a psychiatrist-viewer, it’s a good question to ask!
Dr. Stutz reassures Jonah that it is okay to be vulnerable. “Failure, weakness, vulnerability – it’s like a connector, it connects you to the rest of the world.” A super-sized cardboard cutout of an obese 14-year-old Jonah now joins the room, and we learn that he continues to struggle with his self-image. Things get more real.
Peppered throughout the film, there are lessons from Dr. Stutz about his “tools,” constructs he uses to help people restructure their worlds and take action to move forward. One such construct he calls “the maze,” which occurs when one person in an interpersonal relationship is waiting for fairness and becomes preoccupied with feeling injured.
Jonah inquires about Dr. Stutz’s romantic life and the therapist replies with a transparency that overrides our usual professional boundaries. We all learn that Dr. Stutz is not in a relationship, he’s never been married, but there is a woman he has had some involvement with on and off for 40 years. Jonah’s line of questioning rivals that of any therapist. “How do you think it affects you, having your mom hate men and you being a man?” Dr. Stutz admits that he can never feel safe with women. “Did you ever override that wall you built with your mom and get close to a woman?” When Jonah professes, “I don’t feel anything but love for you and I just want you to be happy,” my own feeling was that the tables had turned too far, that the therapist’s failed romantic life risked being a burden to the patient.
Still, there is something about the relationship between the two men that is touching and beautiful. Dr. Stutz as a therapist is charismatic, caring, self-assured, and optimistic, and he radiates hope and certainty. He mixes an intense intimacy with humor in a way that is both authentic and entertaining. The interspersed jokes break the intensity, but they don’t diminish his wisdom and the healing he imparts.
Dr. Stutz is a psychiatrist, and his strength is clearly as a psychotherapist, yet there is not a single mention of psychotropic medications – there is a banter about recreational drugs and medications for Parkinson’s disease. If Hill is taking medication for depression or anxiety, and if prescribing is part of Dr. Stutz’s arsenal, the viewer is not made aware of this.
Dr. Stutz eschews the slow, detached, and “neutral” pace of psychodynamic therapy and the whole concept of the therapist as a blank wall for the transference to play out on, but here the transference screams: Jonah loves him, he respect and honors him, he wants him to be happy, and he is afraid of losing him.
“Stutz” is a movie about a larger-than-life psychiatrist, one whose warmth and inspiration are healing. I imagine his tools are helpful, but his personality is what carries the load. If a viewer has not had experience with psychiatry, and this film inspires him to begin therapy, there may be a good deal of disappointment. In this case, the patient is a successful actor, and one might wonder if that, together with the entire years-long project of filming, has altered the relationship well beyond the usual therapeutic hour.
Dr. Miller is a coauthor of “Committed: The Battle Over Involuntary Psychiatric Care” (Baltimore: Johns Hopkins University Press, 2016). She has a private practice and is an assistant professor of psychiatry and behavioral sciences at Johns Hopkins University in Baltimore.
Surgical management of borderline ovarian tumors, part 1
Borderline ovarian tumors (BOTs) are estimated to comprise 10%-15% of all epithelial tumors of the ovary. They are characterized by their behavior, which falls somewhere between benign ovarian masses and frank carcinomas. They have cytologic characteristics suggesting malignancy, such as higher cellular proliferation and more variable nuclear atypia, but, unlike carcinomas, they lack destructive stromal invasion. For decades after their recognition by the International Federation of Gynecology and Obstetrics in 1971, these tumors were classified as being of low malignant potential (and subsequently referred to as LMP tumors of the ovary). Beginning with the 2014 World Health Organization classification, the recommended terminology is now borderline tumor of the ovary.
The primary treatment for BOTs is surgery. With a mean age at diagnosis in the fifth decade, many patients with BOTs desire ovarian preservation to maintain fertility and/or prevent surgical menopause. This raises multiple questions regarding the use of fertility-sparing surgery for BOTs: What types of procedures are safe and should be offered? For those patients who undergo fertility-sparing surgery initially, is additional surgery indicated after completion of childbearing or at an age closer to natural menopause? What should this completion surgery include?
Ovarian-sparing surgery
The diagnosis of a BOT is frequently only confirmed after the decision for ovarian conservation has been made. What should be considered before electing to proceed with ovarian cystectomy instead of unilateral salpingo-oophorectomy (USO)?
Is the risk of recurrence higher with cystectomy versus oophorectomy?
Yes. The risk of recurrence of BOT appears to be higher after cystectomy than it is after oophorectomy. There is a large range reported in the literature, with the risk of recurrence after cystectomy described as between 12% and 58%. Most studies report recurrences between 25% and 35% of patients who undergo cystectomy. In contrast, the risk of recurrence after USO is often reported to be approximately 10%. Higher risk of recurrence after cystectomy is speculated to be due to leaving some BOT at the time of initial surgery.
Multiple meta-analyses have found an increased risk of recurrence after cystectomy. The risk of recurrence after unilateral cystectomy was 19.4%, compared with 9.1% after USO, in 2,145 patients included in a 2017 meta-analysis.1 Similarly, a 2021 meta-analysis found a significantly higher rate of BOT recurrence in patients who underwent unilateral or bilateral cystectomy compared with USO (odds ratio, 2.02; 95% confidence interval, 1.59-2.57).2
Does the higher recurrence risk translate into a difference in long-term outcomes?
No. Despite an increased risk of recurrence after cystectomy, ovarian-sparing surgery does not appear to alter patients’ survival. The pooled mortality estimate was 1.6% for those undergoing fertility-sparing surgery (95% CI, 0.011-0.023), compared with 2.0% for those undergoing radical surgery (95% CI, 0.014-0.029), in a 2015 meta-analysis of over 5,100 patients. The analysis included studies in which patients underwent unilateral cystectomy, bilateral cystectomy, USO, or USO plus contralateral cystectomy. The low mortality rate did not allow for comparison between the different types of fertility-sparing surgeries.3
Do we accept a higher risk of recurrence with ovarian sparing surgery to improve fertility?
Data are mixed. When we examine studies describing fertility rates after conservative surgery, there are significant limitations to interpreting the data available. Some studies do not differentiate among patients who underwent fertility-sparing surgery, or between those who had cystectomy versus USO. Other studies do not report the number of patients who tried to achieve pregnancy after surgery. Conception rates are reported to be as high as 88.2%, which was in 116 patients who were able to be reached after fertility-sparing surgery (retained at least one ovary). Of the 51 patients who tried to conceive, 45 were successful.4
Multiple studies and meta-analyses have shown no difference in postoperative pregnancy rates when comparing oophorectomy to cystectomy. For instance, in a 2021 meta-analysis, there was no significant difference noted in pregnancy rates between patients who underwent USO versus cystectomy (OR, 0.92; 95% CI, 0.60-1.42).
There are some data that support improved postoperative pregnancy rates in more conservative surgery, especially in the setting of bilateral BOT. In a small study of 32 patients who had laparoscopic staging for bilateral BOTs, patients were randomized to unilateral oophorectomy plus contralateral cystectomy or to bilateral cystectomy, which was referred to as ultraconservative surgery. The time to first recurrence was shorter in the ultraconservative group (although this lost significance when regression analysis was performed), but the time to first live birth was shorter and the relative chance of having a baby was higher in the bilateral cystectomy group.5
Ovarian-sparing procedures should be offered to patients in the setting of BOT. With ovarian-sparing surgery, it is important to counsel patients about the increased risk of recurrence and need for long-term follow-up. Pregnancy rates are generally good after fertility-sparing surgery. Surgery to conserve both ovaries does not seem to improve pregnancy rates in the setting of unilateral BOTs.
Dr. Tucker is assistant professor of gynecologic oncology at the University of North Carolina at Chapel Hill.
References
1. Jiao X et al. Int J Gynecol Cancer. 2017 Nov;27(9):1833-41.
2. Wang P and Fang L. World J Surg Oncol. 2021 Apr 21;19(1):132.
3. Vasconcelos I and de Sousa Mendes M. Eur J Cancer. 2015 Mar;51(5):620-31.
4. Song T et al. Int J Gynecol Cancer. 2011 May;21(4):640-6.
5. Palomba S et al. Hum Reprod. 2010 Aug;25(8):1966-72.
Borderline ovarian tumors (BOTs) are estimated to comprise 10%-15% of all epithelial tumors of the ovary. They are characterized by their behavior, which falls somewhere between benign ovarian masses and frank carcinomas. They have cytologic characteristics suggesting malignancy, such as higher cellular proliferation and more variable nuclear atypia, but, unlike carcinomas, they lack destructive stromal invasion. For decades after their recognition by the International Federation of Gynecology and Obstetrics in 1971, these tumors were classified as being of low malignant potential (and subsequently referred to as LMP tumors of the ovary). Beginning with the 2014 World Health Organization classification, the recommended terminology is now borderline tumor of the ovary.
The primary treatment for BOTs is surgery. With a mean age at diagnosis in the fifth decade, many patients with BOTs desire ovarian preservation to maintain fertility and/or prevent surgical menopause. This raises multiple questions regarding the use of fertility-sparing surgery for BOTs: What types of procedures are safe and should be offered? For those patients who undergo fertility-sparing surgery initially, is additional surgery indicated after completion of childbearing or at an age closer to natural menopause? What should this completion surgery include?
Ovarian-sparing surgery
The diagnosis of a BOT is frequently only confirmed after the decision for ovarian conservation has been made. What should be considered before electing to proceed with ovarian cystectomy instead of unilateral salpingo-oophorectomy (USO)?
Is the risk of recurrence higher with cystectomy versus oophorectomy?
Yes. The risk of recurrence of BOT appears to be higher after cystectomy than it is after oophorectomy. There is a large range reported in the literature, with the risk of recurrence after cystectomy described as between 12% and 58%. Most studies report recurrences between 25% and 35% of patients who undergo cystectomy. In contrast, the risk of recurrence after USO is often reported to be approximately 10%. Higher risk of recurrence after cystectomy is speculated to be due to leaving some BOT at the time of initial surgery.
Multiple meta-analyses have found an increased risk of recurrence after cystectomy. The risk of recurrence after unilateral cystectomy was 19.4%, compared with 9.1% after USO, in 2,145 patients included in a 2017 meta-analysis.1 Similarly, a 2021 meta-analysis found a significantly higher rate of BOT recurrence in patients who underwent unilateral or bilateral cystectomy compared with USO (odds ratio, 2.02; 95% confidence interval, 1.59-2.57).2
Does the higher recurrence risk translate into a difference in long-term outcomes?
No. Despite an increased risk of recurrence after cystectomy, ovarian-sparing surgery does not appear to alter patients’ survival. The pooled mortality estimate was 1.6% for those undergoing fertility-sparing surgery (95% CI, 0.011-0.023), compared with 2.0% for those undergoing radical surgery (95% CI, 0.014-0.029), in a 2015 meta-analysis of over 5,100 patients. The analysis included studies in which patients underwent unilateral cystectomy, bilateral cystectomy, USO, or USO plus contralateral cystectomy. The low mortality rate did not allow for comparison between the different types of fertility-sparing surgeries.3
Do we accept a higher risk of recurrence with ovarian sparing surgery to improve fertility?
Data are mixed. When we examine studies describing fertility rates after conservative surgery, there are significant limitations to interpreting the data available. Some studies do not differentiate among patients who underwent fertility-sparing surgery, or between those who had cystectomy versus USO. Other studies do not report the number of patients who tried to achieve pregnancy after surgery. Conception rates are reported to be as high as 88.2%, which was in 116 patients who were able to be reached after fertility-sparing surgery (retained at least one ovary). Of the 51 patients who tried to conceive, 45 were successful.4
Multiple studies and meta-analyses have shown no difference in postoperative pregnancy rates when comparing oophorectomy to cystectomy. For instance, in a 2021 meta-analysis, there was no significant difference noted in pregnancy rates between patients who underwent USO versus cystectomy (OR, 0.92; 95% CI, 0.60-1.42).
There are some data that support improved postoperative pregnancy rates in more conservative surgery, especially in the setting of bilateral BOT. In a small study of 32 patients who had laparoscopic staging for bilateral BOTs, patients were randomized to unilateral oophorectomy plus contralateral cystectomy or to bilateral cystectomy, which was referred to as ultraconservative surgery. The time to first recurrence was shorter in the ultraconservative group (although this lost significance when regression analysis was performed), but the time to first live birth was shorter and the relative chance of having a baby was higher in the bilateral cystectomy group.5
Ovarian-sparing procedures should be offered to patients in the setting of BOT. With ovarian-sparing surgery, it is important to counsel patients about the increased risk of recurrence and need for long-term follow-up. Pregnancy rates are generally good after fertility-sparing surgery. Surgery to conserve both ovaries does not seem to improve pregnancy rates in the setting of unilateral BOTs.
Dr. Tucker is assistant professor of gynecologic oncology at the University of North Carolina at Chapel Hill.
References
1. Jiao X et al. Int J Gynecol Cancer. 2017 Nov;27(9):1833-41.
2. Wang P and Fang L. World J Surg Oncol. 2021 Apr 21;19(1):132.
3. Vasconcelos I and de Sousa Mendes M. Eur J Cancer. 2015 Mar;51(5):620-31.
4. Song T et al. Int J Gynecol Cancer. 2011 May;21(4):640-6.
5. Palomba S et al. Hum Reprod. 2010 Aug;25(8):1966-72.
Borderline ovarian tumors (BOTs) are estimated to comprise 10%-15% of all epithelial tumors of the ovary. They are characterized by their behavior, which falls somewhere between benign ovarian masses and frank carcinomas. They have cytologic characteristics suggesting malignancy, such as higher cellular proliferation and more variable nuclear atypia, but, unlike carcinomas, they lack destructive stromal invasion. For decades after their recognition by the International Federation of Gynecology and Obstetrics in 1971, these tumors were classified as being of low malignant potential (and subsequently referred to as LMP tumors of the ovary). Beginning with the 2014 World Health Organization classification, the recommended terminology is now borderline tumor of the ovary.
The primary treatment for BOTs is surgery. With a mean age at diagnosis in the fifth decade, many patients with BOTs desire ovarian preservation to maintain fertility and/or prevent surgical menopause. This raises multiple questions regarding the use of fertility-sparing surgery for BOTs: What types of procedures are safe and should be offered? For those patients who undergo fertility-sparing surgery initially, is additional surgery indicated after completion of childbearing or at an age closer to natural menopause? What should this completion surgery include?
Ovarian-sparing surgery
The diagnosis of a BOT is frequently only confirmed after the decision for ovarian conservation has been made. What should be considered before electing to proceed with ovarian cystectomy instead of unilateral salpingo-oophorectomy (USO)?
Is the risk of recurrence higher with cystectomy versus oophorectomy?
Yes. The risk of recurrence of BOT appears to be higher after cystectomy than it is after oophorectomy. There is a large range reported in the literature, with the risk of recurrence after cystectomy described as between 12% and 58%. Most studies report recurrences between 25% and 35% of patients who undergo cystectomy. In contrast, the risk of recurrence after USO is often reported to be approximately 10%. Higher risk of recurrence after cystectomy is speculated to be due to leaving some BOT at the time of initial surgery.
Multiple meta-analyses have found an increased risk of recurrence after cystectomy. The risk of recurrence after unilateral cystectomy was 19.4%, compared with 9.1% after USO, in 2,145 patients included in a 2017 meta-analysis.1 Similarly, a 2021 meta-analysis found a significantly higher rate of BOT recurrence in patients who underwent unilateral or bilateral cystectomy compared with USO (odds ratio, 2.02; 95% confidence interval, 1.59-2.57).2
Does the higher recurrence risk translate into a difference in long-term outcomes?
No. Despite an increased risk of recurrence after cystectomy, ovarian-sparing surgery does not appear to alter patients’ survival. The pooled mortality estimate was 1.6% for those undergoing fertility-sparing surgery (95% CI, 0.011-0.023), compared with 2.0% for those undergoing radical surgery (95% CI, 0.014-0.029), in a 2015 meta-analysis of over 5,100 patients. The analysis included studies in which patients underwent unilateral cystectomy, bilateral cystectomy, USO, or USO plus contralateral cystectomy. The low mortality rate did not allow for comparison between the different types of fertility-sparing surgeries.3
Do we accept a higher risk of recurrence with ovarian sparing surgery to improve fertility?
Data are mixed. When we examine studies describing fertility rates after conservative surgery, there are significant limitations to interpreting the data available. Some studies do not differentiate among patients who underwent fertility-sparing surgery, or between those who had cystectomy versus USO. Other studies do not report the number of patients who tried to achieve pregnancy after surgery. Conception rates are reported to be as high as 88.2%, which was in 116 patients who were able to be reached after fertility-sparing surgery (retained at least one ovary). Of the 51 patients who tried to conceive, 45 were successful.4
Multiple studies and meta-analyses have shown no difference in postoperative pregnancy rates when comparing oophorectomy to cystectomy. For instance, in a 2021 meta-analysis, there was no significant difference noted in pregnancy rates between patients who underwent USO versus cystectomy (OR, 0.92; 95% CI, 0.60-1.42).
There are some data that support improved postoperative pregnancy rates in more conservative surgery, especially in the setting of bilateral BOT. In a small study of 32 patients who had laparoscopic staging for bilateral BOTs, patients were randomized to unilateral oophorectomy plus contralateral cystectomy or to bilateral cystectomy, which was referred to as ultraconservative surgery. The time to first recurrence was shorter in the ultraconservative group (although this lost significance when regression analysis was performed), but the time to first live birth was shorter and the relative chance of having a baby was higher in the bilateral cystectomy group.5
Ovarian-sparing procedures should be offered to patients in the setting of BOT. With ovarian-sparing surgery, it is important to counsel patients about the increased risk of recurrence and need for long-term follow-up. Pregnancy rates are generally good after fertility-sparing surgery. Surgery to conserve both ovaries does not seem to improve pregnancy rates in the setting of unilateral BOTs.
Dr. Tucker is assistant professor of gynecologic oncology at the University of North Carolina at Chapel Hill.
References
1. Jiao X et al. Int J Gynecol Cancer. 2017 Nov;27(9):1833-41.
2. Wang P and Fang L. World J Surg Oncol. 2021 Apr 21;19(1):132.
3. Vasconcelos I and de Sousa Mendes M. Eur J Cancer. 2015 Mar;51(5):620-31.
4. Song T et al. Int J Gynecol Cancer. 2011 May;21(4):640-6.
5. Palomba S et al. Hum Reprod. 2010 Aug;25(8):1966-72.
What happens when newer weight loss meds are stopped?
Some of these medicines are approved for treating obesity (Wegovy), whereas others are approved for type 2 diabetes (Ozempic and Mounjaro). Tirzepatide (Mounjaro) has been fast-tracked for approval for weight loss by the U.S. Food and Drug Administration this year, and in the first of the series of studies looking at its effect on obesity, the SURMOUNT-1 trial, tirzepatide demonstrated a mean weight loss of around 22% in people without diabetes, spurring significant off-label use.
Our offices are full of patients who have taken these medications, with unprecedented improvements in their weight, cardiometabolic health, and quality of life. What happens when patients stop taking these medications? Or more importantly, why stop them?
Although these drugs are very effective for weight loss and treating diabetes, there can be adverse effects, primarily gastrointestinal, that limit treatment continuation. Nausea is the most common side effect and usually diminishes over time. Slow dose titration and dietary modification can minimize unwanted gastrointestinal side effects.
Drug-induced acute pancreatitis, a rare adverse event requiring patients to stop therapy, was seen in approximately 0.2% of people in clinical trials.
Medications effective but cost prohibitive?
Beyond adverse effects, patients may be forced to stop treatment because of medication cost, changes in insurance coverage, or issues with drug availability.
Two incretin therapies currently approved for treating obesity – liraglutide (Saxenda) and semaglutide (Wegovy) – cost around $1,400 per month. Insurance coverage and manufacturer discounts can make treatment affordable, but anti-obesity medicines aren’t covered by Medicare or by many employer-sponsored commercial plans.
Changes in employment or insurance coverage, or expiration of manufacturer copay cards, may require patients to stop or change therapies. The increased prescribing and overall expense of these drugs have prompted insurance plans and self-insured groups to consider whether providing coverage for these medications is sustainable.
Limited coverage has led to significant off-label prescribing of incretin therapies that aren’t approved for treating obesity (for instance, Ozempic and Mounjaro) and compounding pharmacies selling peptides that allegedly contain the active pharmaceutical ingredients. High demand for these medications has created significant supply shortages over the past year, causing many people to be without treatment for significant periods of time, as reported by this news organization.
Recently, I saw a patient who lost more than 30 pounds with semaglutide (Wegovy). She then changed employers and the medication was no longer covered. She gained back almost 10 pounds over 3 months and was prescribed tirzepatide (Mounjaro) off-label for weight loss by another provider, using a manufacturer discount card to make the medication affordable. The patient did well with the new regimen and lost about 20 pounds, but the pharmacy stopped filling the prescription when changes were made to the discount card. Afraid of regaining the weight, she came to see us as a new patient to discuss her options with her lack of coverage for anti-obesity medications.
Stopping equals weight regain
Obesity is a chronic disease like hypertension. It responds to treatment and when people stop taking these anti-obesity medications, this is generally associated with increased appetite and less satiety, and there is subsequent weight regain and a recurrence in excess weight-related complications.
The STEP-1 trial extension showed an initial mean body weight reduction of 17.3% with weekly semaglutide 2.4 mg over 1 year. On average, two-thirds of the weight lost was regained by participants within 1 year of stopping semaglutide and the study’s lifestyle intervention. Many of the improvements seen in cardiometabolic variables, like blood glucose and blood pressure, similarly reverted to baseline.
There are also 2-year data from the STEP-5 trial with semaglutide; 3-year data from the SCALE trial with liraglutide; and 5-year nonrandomized data with multiple agents that show durable, clinically significant weight loss from medical therapies for obesity.
These data together demonstrate that medications are effective for durable weight loss if they are continued. However, this is not how obesity is currently treated. Anti-obesity medications are prescribed to less than 3% of eligible people in the United States, and the average duration of therapy is less than 90 days. This treatment length isn’t sufficient to see the full benefits most medications offer and certainly doesn’t support long-term weight maintenance.
A recent study showed that, in addition to maintaining weight loss from medical therapies, incretin-containing anti-obesity medication regimens were effective for treating weight regain and facilitating healthier weight after bariatric surgery.
Chronic therapy is needed for weight maintenance because several neurohormonal changes occur owing to weight loss. Metabolic adaptation is the relative reduction in energy expenditure, below what would be expected, in people after weight loss. When this is combined with physiologic changes that increase appetite and decrease satiety, many people create a positive energy balance that results in weight regain. This has been observed in reality TV shows such as “The Biggest Loser”: It’s biology, not willpower.
Unfortunately, many people – including health care providers – don’t understand how these changes promote weight regain and patients are too often blamed when their weight goes back up after medications are stopped. This blame is greatly misinformed by weight-biased beliefs that people with obesity are lazy and lack self-control for weight loss or maintenance. Nobody would be surprised if someone’s blood pressure went up if their antihypertensive medications were stopped. Why do we think so differently when treating obesity?
The prevalence of obesity in the United States is over 40% and growing. We are fortunate to have new medications that on average lead to 15% or greater weight loss when combined with lifestyle modification.
However, these medications are expensive and the limited insurance coverage currently available may not improve. From a patient experience perspective, it’s distressing to have to discontinue treatments that have helped to achieve a healthier weight and then experience regain.
People need better access to evidence-based treatments for obesity, which include lifestyle interventions, anti-obesity medications, and bariatric procedures. Successful treatment of obesity should include a personalized, patient-centered approach that may require a combination of therapies, such as medications and surgery, for lasting weight control.
Dr. Almandoz is associate professor, department of internal medicine, division of endocrinology; medical director, weight wellness program, University of Texas Southwestern, Dallas. He disclosed ties with Novo Nordisk and Eli Lilly. Follow Dr. Almandoz on Twitter: @JaimeAlmandoz.
A version of this article originally appeared on Medscape.com.
Some of these medicines are approved for treating obesity (Wegovy), whereas others are approved for type 2 diabetes (Ozempic and Mounjaro). Tirzepatide (Mounjaro) has been fast-tracked for approval for weight loss by the U.S. Food and Drug Administration this year, and in the first of the series of studies looking at its effect on obesity, the SURMOUNT-1 trial, tirzepatide demonstrated a mean weight loss of around 22% in people without diabetes, spurring significant off-label use.
Our offices are full of patients who have taken these medications, with unprecedented improvements in their weight, cardiometabolic health, and quality of life. What happens when patients stop taking these medications? Or more importantly, why stop them?
Although these drugs are very effective for weight loss and treating diabetes, there can be adverse effects, primarily gastrointestinal, that limit treatment continuation. Nausea is the most common side effect and usually diminishes over time. Slow dose titration and dietary modification can minimize unwanted gastrointestinal side effects.
Drug-induced acute pancreatitis, a rare adverse event requiring patients to stop therapy, was seen in approximately 0.2% of people in clinical trials.
Medications effective but cost prohibitive?
Beyond adverse effects, patients may be forced to stop treatment because of medication cost, changes in insurance coverage, or issues with drug availability.
Two incretin therapies currently approved for treating obesity – liraglutide (Saxenda) and semaglutide (Wegovy) – cost around $1,400 per month. Insurance coverage and manufacturer discounts can make treatment affordable, but anti-obesity medicines aren’t covered by Medicare or by many employer-sponsored commercial plans.
Changes in employment or insurance coverage, or expiration of manufacturer copay cards, may require patients to stop or change therapies. The increased prescribing and overall expense of these drugs have prompted insurance plans and self-insured groups to consider whether providing coverage for these medications is sustainable.
Limited coverage has led to significant off-label prescribing of incretin therapies that aren’t approved for treating obesity (for instance, Ozempic and Mounjaro) and compounding pharmacies selling peptides that allegedly contain the active pharmaceutical ingredients. High demand for these medications has created significant supply shortages over the past year, causing many people to be without treatment for significant periods of time, as reported by this news organization.
Recently, I saw a patient who lost more than 30 pounds with semaglutide (Wegovy). She then changed employers and the medication was no longer covered. She gained back almost 10 pounds over 3 months and was prescribed tirzepatide (Mounjaro) off-label for weight loss by another provider, using a manufacturer discount card to make the medication affordable. The patient did well with the new regimen and lost about 20 pounds, but the pharmacy stopped filling the prescription when changes were made to the discount card. Afraid of regaining the weight, she came to see us as a new patient to discuss her options with her lack of coverage for anti-obesity medications.
Stopping equals weight regain
Obesity is a chronic disease like hypertension. It responds to treatment and when people stop taking these anti-obesity medications, this is generally associated with increased appetite and less satiety, and there is subsequent weight regain and a recurrence in excess weight-related complications.
The STEP-1 trial extension showed an initial mean body weight reduction of 17.3% with weekly semaglutide 2.4 mg over 1 year. On average, two-thirds of the weight lost was regained by participants within 1 year of stopping semaglutide and the study’s lifestyle intervention. Many of the improvements seen in cardiometabolic variables, like blood glucose and blood pressure, similarly reverted to baseline.
There are also 2-year data from the STEP-5 trial with semaglutide; 3-year data from the SCALE trial with liraglutide; and 5-year nonrandomized data with multiple agents that show durable, clinically significant weight loss from medical therapies for obesity.
These data together demonstrate that medications are effective for durable weight loss if they are continued. However, this is not how obesity is currently treated. Anti-obesity medications are prescribed to less than 3% of eligible people in the United States, and the average duration of therapy is less than 90 days. This treatment length isn’t sufficient to see the full benefits most medications offer and certainly doesn’t support long-term weight maintenance.
A recent study showed that, in addition to maintaining weight loss from medical therapies, incretin-containing anti-obesity medication regimens were effective for treating weight regain and facilitating healthier weight after bariatric surgery.
Chronic therapy is needed for weight maintenance because several neurohormonal changes occur owing to weight loss. Metabolic adaptation is the relative reduction in energy expenditure, below what would be expected, in people after weight loss. When this is combined with physiologic changes that increase appetite and decrease satiety, many people create a positive energy balance that results in weight regain. This has been observed in reality TV shows such as “The Biggest Loser”: It’s biology, not willpower.
Unfortunately, many people – including health care providers – don’t understand how these changes promote weight regain and patients are too often blamed when their weight goes back up after medications are stopped. This blame is greatly misinformed by weight-biased beliefs that people with obesity are lazy and lack self-control for weight loss or maintenance. Nobody would be surprised if someone’s blood pressure went up if their antihypertensive medications were stopped. Why do we think so differently when treating obesity?
The prevalence of obesity in the United States is over 40% and growing. We are fortunate to have new medications that on average lead to 15% or greater weight loss when combined with lifestyle modification.
However, these medications are expensive and the limited insurance coverage currently available may not improve. From a patient experience perspective, it’s distressing to have to discontinue treatments that have helped to achieve a healthier weight and then experience regain.
People need better access to evidence-based treatments for obesity, which include lifestyle interventions, anti-obesity medications, and bariatric procedures. Successful treatment of obesity should include a personalized, patient-centered approach that may require a combination of therapies, such as medications and surgery, for lasting weight control.
Dr. Almandoz is associate professor, department of internal medicine, division of endocrinology; medical director, weight wellness program, University of Texas Southwestern, Dallas. He disclosed ties with Novo Nordisk and Eli Lilly. Follow Dr. Almandoz on Twitter: @JaimeAlmandoz.
A version of this article originally appeared on Medscape.com.
Some of these medicines are approved for treating obesity (Wegovy), whereas others are approved for type 2 diabetes (Ozempic and Mounjaro). Tirzepatide (Mounjaro) has been fast-tracked for approval for weight loss by the U.S. Food and Drug Administration this year, and in the first of the series of studies looking at its effect on obesity, the SURMOUNT-1 trial, tirzepatide demonstrated a mean weight loss of around 22% in people without diabetes, spurring significant off-label use.
Our offices are full of patients who have taken these medications, with unprecedented improvements in their weight, cardiometabolic health, and quality of life. What happens when patients stop taking these medications? Or more importantly, why stop them?
Although these drugs are very effective for weight loss and treating diabetes, there can be adverse effects, primarily gastrointestinal, that limit treatment continuation. Nausea is the most common side effect and usually diminishes over time. Slow dose titration and dietary modification can minimize unwanted gastrointestinal side effects.
Drug-induced acute pancreatitis, a rare adverse event requiring patients to stop therapy, was seen in approximately 0.2% of people in clinical trials.
Medications effective but cost prohibitive?
Beyond adverse effects, patients may be forced to stop treatment because of medication cost, changes in insurance coverage, or issues with drug availability.
Two incretin therapies currently approved for treating obesity – liraglutide (Saxenda) and semaglutide (Wegovy) – cost around $1,400 per month. Insurance coverage and manufacturer discounts can make treatment affordable, but anti-obesity medicines aren’t covered by Medicare or by many employer-sponsored commercial plans.
Changes in employment or insurance coverage, or expiration of manufacturer copay cards, may require patients to stop or change therapies. The increased prescribing and overall expense of these drugs have prompted insurance plans and self-insured groups to consider whether providing coverage for these medications is sustainable.
Limited coverage has led to significant off-label prescribing of incretin therapies that aren’t approved for treating obesity (for instance, Ozempic and Mounjaro) and compounding pharmacies selling peptides that allegedly contain the active pharmaceutical ingredients. High demand for these medications has created significant supply shortages over the past year, causing many people to be without treatment for significant periods of time, as reported by this news organization.
Recently, I saw a patient who lost more than 30 pounds with semaglutide (Wegovy). She then changed employers and the medication was no longer covered. She gained back almost 10 pounds over 3 months and was prescribed tirzepatide (Mounjaro) off-label for weight loss by another provider, using a manufacturer discount card to make the medication affordable. The patient did well with the new regimen and lost about 20 pounds, but the pharmacy stopped filling the prescription when changes were made to the discount card. Afraid of regaining the weight, she came to see us as a new patient to discuss her options with her lack of coverage for anti-obesity medications.
Stopping equals weight regain
Obesity is a chronic disease like hypertension. It responds to treatment and when people stop taking these anti-obesity medications, this is generally associated with increased appetite and less satiety, and there is subsequent weight regain and a recurrence in excess weight-related complications.
The STEP-1 trial extension showed an initial mean body weight reduction of 17.3% with weekly semaglutide 2.4 mg over 1 year. On average, two-thirds of the weight lost was regained by participants within 1 year of stopping semaglutide and the study’s lifestyle intervention. Many of the improvements seen in cardiometabolic variables, like blood glucose and blood pressure, similarly reverted to baseline.
There are also 2-year data from the STEP-5 trial with semaglutide; 3-year data from the SCALE trial with liraglutide; and 5-year nonrandomized data with multiple agents that show durable, clinically significant weight loss from medical therapies for obesity.
These data together demonstrate that medications are effective for durable weight loss if they are continued. However, this is not how obesity is currently treated. Anti-obesity medications are prescribed to less than 3% of eligible people in the United States, and the average duration of therapy is less than 90 days. This treatment length isn’t sufficient to see the full benefits most medications offer and certainly doesn’t support long-term weight maintenance.
A recent study showed that, in addition to maintaining weight loss from medical therapies, incretin-containing anti-obesity medication regimens were effective for treating weight regain and facilitating healthier weight after bariatric surgery.
Chronic therapy is needed for weight maintenance because several neurohormonal changes occur owing to weight loss. Metabolic adaptation is the relative reduction in energy expenditure, below what would be expected, in people after weight loss. When this is combined with physiologic changes that increase appetite and decrease satiety, many people create a positive energy balance that results in weight regain. This has been observed in reality TV shows such as “The Biggest Loser”: It’s biology, not willpower.
Unfortunately, many people – including health care providers – don’t understand how these changes promote weight regain and patients are too often blamed when their weight goes back up after medications are stopped. This blame is greatly misinformed by weight-biased beliefs that people with obesity are lazy and lack self-control for weight loss or maintenance. Nobody would be surprised if someone’s blood pressure went up if their antihypertensive medications were stopped. Why do we think so differently when treating obesity?
The prevalence of obesity in the United States is over 40% and growing. We are fortunate to have new medications that on average lead to 15% or greater weight loss when combined with lifestyle modification.
However, these medications are expensive and the limited insurance coverage currently available may not improve. From a patient experience perspective, it’s distressing to have to discontinue treatments that have helped to achieve a healthier weight and then experience regain.
People need better access to evidence-based treatments for obesity, which include lifestyle interventions, anti-obesity medications, and bariatric procedures. Successful treatment of obesity should include a personalized, patient-centered approach that may require a combination of therapies, such as medications and surgery, for lasting weight control.
Dr. Almandoz is associate professor, department of internal medicine, division of endocrinology; medical director, weight wellness program, University of Texas Southwestern, Dallas. He disclosed ties with Novo Nordisk and Eli Lilly. Follow Dr. Almandoz on Twitter: @JaimeAlmandoz.
A version of this article originally appeared on Medscape.com.
The desk
Recently, Dr. Jeffrey Benabio (I don’t believe we’ve ever met), wrote an enjoyable commentary mourning the loss of letters – the wonderful paper-and-pen documents that were, for the vast majority of human history, the main method of long distance communication. Even today, he notes, there’s something special about a letter, with the time and human effort required to sit down and put pen to paper, seal it into an envelope, and entrust it to the post office.
In his piece, Dr. Benabio describes his work desk as “a small surface, perhaps just enough for the monitor and a mug ... it has no drawers. It is lean and immaculate, but it has no soul.”
With all due respect, I can’t do that. I need a desk to function. A REAL one.
I was 9 when I got my first desk, far more than a 4th-grader needed. My dad was an attorney and had an extra desk from a partner who’d retired. It was big and heavy and made of wood. It had three drawers on each side, one in the middle, and pull-outs on each side in case you needed even more writing space. I loved it. As the years went by I did homework, wrote short stories, and built models on it. I covered the pull-outs with stickers for starship controls, so on a whim I could jump to hyperspace. In 1984 a brand-new Apple Macintosh, with 128K of RAM showed up on it. I began using the computer to write college papers, but most of my work at the desk still involved books and handwriting.
My current home desk has been with me through college, medical school, residency, and fellowship, and it continues with me today.
At my office, though, is my main desk. Before 2013 I was in a small back office, with only room for a tiny three-drawer college desk.
But in 2013 I moved into my own office, for the first time in my career. Now it was time to bring in my real desk, waiting in storage since my Dad had retired.
This is my desk now. It’s huge. It’s heavy. My dad bought it when he started his law practice in 1968. It has eight drawers, and my Dad’s original leather blotter is on top. It came with his chrome and brass letter opener in the top drawer. It has space for my computer, writing pads, exam tools (for people who can’t get on the exam table across the hall), business cards, a few baubles from my kids, stapler, tape dispenser, pen cup, phone, coffee mug, and a million other things.
It takes up a lot of space, but I don’t mind. There’s a human comfort to it and the organized disorder on top of it.
Everyone practices medicine differently. What works for me isn’t going to work for another doctor, and definitely not for another specialty.
But here, the big desk is part of my personal style. Sitting there gets me into “doctor mode” each day. I hope the more casual surroundings make it comfortable for patients, too.
It’s part of the soul of my practice, and I wouldn’t have it any other way.
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
Recently, Dr. Jeffrey Benabio (I don’t believe we’ve ever met), wrote an enjoyable commentary mourning the loss of letters – the wonderful paper-and-pen documents that were, for the vast majority of human history, the main method of long distance communication. Even today, he notes, there’s something special about a letter, with the time and human effort required to sit down and put pen to paper, seal it into an envelope, and entrust it to the post office.
In his piece, Dr. Benabio describes his work desk as “a small surface, perhaps just enough for the monitor and a mug ... it has no drawers. It is lean and immaculate, but it has no soul.”
With all due respect, I can’t do that. I need a desk to function. A REAL one.
I was 9 when I got my first desk, far more than a 4th-grader needed. My dad was an attorney and had an extra desk from a partner who’d retired. It was big and heavy and made of wood. It had three drawers on each side, one in the middle, and pull-outs on each side in case you needed even more writing space. I loved it. As the years went by I did homework, wrote short stories, and built models on it. I covered the pull-outs with stickers for starship controls, so on a whim I could jump to hyperspace. In 1984 a brand-new Apple Macintosh, with 128K of RAM showed up on it. I began using the computer to write college papers, but most of my work at the desk still involved books and handwriting.
My current home desk has been with me through college, medical school, residency, and fellowship, and it continues with me today.
At my office, though, is my main desk. Before 2013 I was in a small back office, with only room for a tiny three-drawer college desk.
But in 2013 I moved into my own office, for the first time in my career. Now it was time to bring in my real desk, waiting in storage since my Dad had retired.
This is my desk now. It’s huge. It’s heavy. My dad bought it when he started his law practice in 1968. It has eight drawers, and my Dad’s original leather blotter is on top. It came with his chrome and brass letter opener in the top drawer. It has space for my computer, writing pads, exam tools (for people who can’t get on the exam table across the hall), business cards, a few baubles from my kids, stapler, tape dispenser, pen cup, phone, coffee mug, and a million other things.
It takes up a lot of space, but I don’t mind. There’s a human comfort to it and the organized disorder on top of it.
Everyone practices medicine differently. What works for me isn’t going to work for another doctor, and definitely not for another specialty.
But here, the big desk is part of my personal style. Sitting there gets me into “doctor mode” each day. I hope the more casual surroundings make it comfortable for patients, too.
It’s part of the soul of my practice, and I wouldn’t have it any other way.
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
Recently, Dr. Jeffrey Benabio (I don’t believe we’ve ever met), wrote an enjoyable commentary mourning the loss of letters – the wonderful paper-and-pen documents that were, for the vast majority of human history, the main method of long distance communication. Even today, he notes, there’s something special about a letter, with the time and human effort required to sit down and put pen to paper, seal it into an envelope, and entrust it to the post office.
In his piece, Dr. Benabio describes his work desk as “a small surface, perhaps just enough for the monitor and a mug ... it has no drawers. It is lean and immaculate, but it has no soul.”
With all due respect, I can’t do that. I need a desk to function. A REAL one.
I was 9 when I got my first desk, far more than a 4th-grader needed. My dad was an attorney and had an extra desk from a partner who’d retired. It was big and heavy and made of wood. It had three drawers on each side, one in the middle, and pull-outs on each side in case you needed even more writing space. I loved it. As the years went by I did homework, wrote short stories, and built models on it. I covered the pull-outs with stickers for starship controls, so on a whim I could jump to hyperspace. In 1984 a brand-new Apple Macintosh, with 128K of RAM showed up on it. I began using the computer to write college papers, but most of my work at the desk still involved books and handwriting.
My current home desk has been with me through college, medical school, residency, and fellowship, and it continues with me today.
At my office, though, is my main desk. Before 2013 I was in a small back office, with only room for a tiny three-drawer college desk.
But in 2013 I moved into my own office, for the first time in my career. Now it was time to bring in my real desk, waiting in storage since my Dad had retired.
This is my desk now. It’s huge. It’s heavy. My dad bought it when he started his law practice in 1968. It has eight drawers, and my Dad’s original leather blotter is on top. It came with his chrome and brass letter opener in the top drawer. It has space for my computer, writing pads, exam tools (for people who can’t get on the exam table across the hall), business cards, a few baubles from my kids, stapler, tape dispenser, pen cup, phone, coffee mug, and a million other things.
It takes up a lot of space, but I don’t mind. There’s a human comfort to it and the organized disorder on top of it.
Everyone practices medicine differently. What works for me isn’t going to work for another doctor, and definitely not for another specialty.
But here, the big desk is part of my personal style. Sitting there gets me into “doctor mode” each day. I hope the more casual surroundings make it comfortable for patients, too.
It’s part of the soul of my practice, and I wouldn’t have it any other way.
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
Headache before the revolution: A clinician looks back
Headache treatment before the early 1990s was marked by decades of improvisation with mostly unapproved agents, followed by an explosion of scientific interest and new treatments developed specifically for migraine.
But this is largely thanks to the sea change that occurred 30 years ago.
In an interview, Alan M. Rapoport, MD, editor-in-chief of Neurology Reviews, past president of the International Headache Society and clinical professor of neurology at UCLA’s David Geffen School of Medicine in Los Angeles, recalled what it was like to treat patients before and after triptan medications came onto the market.
After the first of these anti-migraine agents, sumatriptan, was approved by the Food and Drug Administration in late December 1992, headache specialists found themselves with a powerful, approved treatment that validated their commitment to solving the disorder, and helped put to rest a persistent but mistaken notion that migraine was a psychiatric condition affecting young women.
But in the 1970s and 1980s, “there wasn’t great science explaining the pathophysiology of common primary headaches like tension-type headache, cluster headache, and migraine,” Dr. Rapoport recalled. “There is often comorbid depression and anxiety with migraine, and sometimes more serious psychiatric disease, but it doesn’t mean migraine is caused by psychological issues. Now we see it clearly as a disease of the brain, but it took years of investigation to prove that.”
The early years
Dr. Rapoport’s journey with headache began in 1972, when he joined a private neurology practice in Stamford and Greenwich, Conn. Neurologists were frowned upon then for having too much interest in headache, he said. There was poor remuneration for doctors treating headache patients, who were hard to properly diagnose and effectively care for. Few medications could effectively stop a migraine attack or reliably reduce the frequency of headaches or the disability they caused.
On weekends Dr. Rapoport covered emergency departments and ICUs at three hospitals, where standard treatment for a migraine attack was injectable opiates. Not only did this treatment aggravate nausea, a common migraine symptom, “but it did not stop the migraine process.” Once the pain relief wore off, patients woke up with the same headache, Dr. Rapoport recalled. “The other drug that was available was ergotamine tartrate” – a fungal alkaloid used since medieval times to treat headache – “given sublingually. It helped the headache slightly but increased the nausea. DHE, or dihydroergotamine, was available only by injection and not used very much.”
DHE, a semi-synthetic molecule based on ergotamine, had FDA approval for migraine, but was complicated to administer. Like the opioids, it provoked vomiting when given intravenously, in patients already suffering migraine-induced nausea. But Dr. Rapoport, along with some of his colleagues, felt that there was a role for DHE for the most severe subtypes of patients, those with long histories of frequent migraines.
“We put people in the hospital and we gave them intravenous DHE. Eventually I got the idea to give it intramuscularly or subcutaneously in the emergency room or my office. When you give it that way, it doesn’t work as quickly but has fewer side effects.” Dr. Rapoport designed a cocktail by coadministering promethazine for nausea, and eventually added a steroid, dexamethasone. The triple shots worked on most patients experiencing severe daily or near-daily migraine attacks, Dr. Rapoport saw, and he began administering the drug combination at The New England Center for Headache in Stamford and Greenwich, Conn., which he opened with Dr. Fred D. Sheftell in 1979.
“The triple shots really worked,” Dr. Rapoport recalled. “There was no need to keep patients in the office or emergency room for intravenous therapy. The patients never called to complain or came back the next day,” he said, as often occurred with opioid treatment.
Dr. Rapoport had learned early in his residency, in the late 1960s, from Dr. David R. Coddon, a neurologist at Mount Sinai hospital in New York, that a tricyclic antidepressant, imipramine, could be helpful in some patients with frequent migraine attacks. As evidence trickled in that other antidepressants, beta-blockers, and antiepileptic drugs might have preventive properties, Dr. Rapoport and others prescribed them for certain patients. But of all the drugs in the headache specialists’ repertoire, few were approved for either treatment or prevention. “And this continued until the triptans,” Dr. Rapoport said.
The triptan era
Sumatriptan was developed by Glaxo for the acute treatment of migraine. The medication, first available only as self-administered subcutaneous injections, was originally designed to bind to vascular serotonin receptors to allow selective constriction of cranial vessels that dilate, causing pain, during a migraine attack. (Years later it was discovered that triptans also worked as anti-inflammatory agents that decreased the release of the neurotransmitter calcitonin gene-related peptide, or CGRP.)
Triptans “changed the world for migraine patients and for me,” Dr. Rapoport said. “I could now prescribe a medication that people could take at home to decrease or stop the migraine process in an hour or two.” The success of the triptans prompted pharmaceutical companies to search for new, more effective ways to treat migraine attacks, with better tolerability.
Seven different triptans were developed, some as injections or tablets and others as nasal sprays. “If one triptan didn’t work, we’d give a second and rarely a third,” Dr. Rapoport said. “We learned that if oral triptans did not work, the most likely issue was that it was not rapidly absorbed from the small intestine, as migraine patients have nausea, poor GI absorption, and slow transit times. This prompted the greater use of injections and nasal sprays.” Headache specialists began combining triptan treatment with nonsteroidal anti-inflammatory drugs, offering further relief for the acute care of migraine.
Medication overuse headache
The years between 1993 and 2000, which saw all the current triptan drugs come onto the market, was an exhilarating one for headache specialists. But even those who were thrilled by the possibilities of the triptans, like Dr. Rapoport, soon came to recognize their limitations, in terms of side effects and poor tolerability for some patients.
Specialists also noticed something unsettling about the triptans: that patients’ headaches seemed to recur within a day, or occur more frequently over time, with higher medication use.
Medication overuse headache (MOH) was known to occur when patients treated migraine too often with acute care medications, especially over-the-counter analgesics and prescription opioids and barbiturates. Dr. Rapoport began warning at conferences and in seminars that MOH seemed to occur with the triptans as well. “In the beginning other doctors didn’t think the triptans could cause MOH, but I observed that patients who were taking triptans daily or almost daily were having increased headache frequency and the triptans stopped being effective. If they didn’t take the drug they were overusing, they were going to get much worse, almost like a withdrawal.”
Today, all seven triptans are now generic, and they remain a mainstay of migraine treatment: “Almost all of my patients are using, or have used a triptan,” Dr. Rapoport said. Yet researchers came to recognize the need for treatments targeting different pathways, both for prevention and acute care.
The next revolution: CGRP and gepants
Studies in the early 2000s began to show a link between the release of one ubiquitous nervous system neurotransmitter, calcitonin gene-related peptide, or CGRP, and migraine. They also noticed that blocking meningeal inflammation could lead to improvement in headache. Two new drug classes emerged from this science: monoclonal antibodies against CGRP or its receptor that had to be given by injection, and oral CGRP receptor blockers that could be used both as a preventive or as an acute care medication.
In 2018 the first monoclonal antibody against the CGRP receptor, erenumab (Aimovig, marketed by Amgen), delivered by injection, was approved for migraine prevention. Three others followed, most given by autoinjector, and one by IV infusion in office or hospital settings. “Those drugs are great,” Dr. Rapoport said. “You take one shot a month or every 3 months, and your headaches drop by 50% or more with very few side effects. Some patients actually see their migraines disappear.”
The following year ubrogepant (Ubrelvy, marketed by AbbVie), the first of a novel class of oral CGRP receptor blockers known as “gepants,” was approved to treat acute migraine. The FDA soon approved another gepant, rimegepant (Nurtec, marketed by Pfizer), which received indications both for prevention and for stopping a migraine attack acutely.
Both classes of therapies – the antibodies and the gepants – are far costlier than the triptans, which are all generic, and may not be needed for every migraine patient. With the gepants, for example, insurers may restrict use to people who have not responded to triptans or for whom triptans are contraindicated or cause too many adverse events. But the CGRP-targeted therapies as a whole “have been every bit as revolutionary” as the triptans, Dr. Rapoport said. The treatments work quickly to resolve headache and disability and get the patient functioning within an hour or two, and there are fewer side effects.
In a review article published in CNS Drugs in 2021, Dr. Rapoport and his colleagues reported that the anti-CGRP treatment with gepants did not appear linked to medication overuse headache, as virtually all previous acute care medication classes did, and could be used in patients who had previously reported MOH. “I am confident that over the next few years, more people will be using them as insurance coverage will improve for patients living with migraine,” he said.
Headache treatment today
Migraine specialists and patients now have a staggering range of therapeutic options. Approved treatments now include prevention of migraine with onabotulinumtoxinA (Botox, marketed by the Allergan division of AbbVie) injections, which work alone and with other medicines; acute care treatment with ditans like lasmiditan (Reyvow, marketed by Lilly*), a category of acute care medicines that work like triptans but target different serotonin receptors. Five devices have been cleared for migraine and other types of headache by the FDA. These work alone or along with medication and can be used acutely or preventively. The devices “should be used more,” Dr. Rapoport said, but are not yet well covered by insurance.
Thirty years after the triptans, scientists and researchers continue to explore the pathophysiology of headache disorders, finding new pathways and identifying new potential targets.
“There are many parts of the brain and brain stem that are involved, as well as the thalamus and hypothalamus,” Dr. Rapoport said. “It’s interesting that the newer medications, and some of the older ones, work in the peripheral nervous system, outside the brain stem in the trigeminovascular system, to modulate the central nervous system. We also know that the CGRP system is involved with cellular second-order messengers. Stimulating and blocking this chain of reactions with newer drugs may become treatments in the future.”
Recent research has focused on a blood vessel dilating neurotransmitter, pituitary adenylate-cyclase-activating polypeptide, or PACAP-38, as a potential therapeutic target. Psychedelic medications such as psilocybin, strong pain medications such as ketamine, and even cannabinoids such as marijuana have all been investigated in migraine. Biofeedback therapies, mindfulness, and other behavioral interventions also have proved effective.
“I expect the next 2-5 years to bring us many important clinical trials on new types of pharmacological treatments,” Dr. Rapoport said. “This is a wonderful time to be a doctor or nurse treating patients living with migraine. When I started out treating headache, 51 years ago, we had only ergotamine tartrate. Today we have so many therapies and combinations of therapies that I hardly know where to start.”
Dr. Rapoport has served as a consultant to or speaker for AbbVie, Amgen, Biohaven, Cala Health, Lundbeck, Satsuma, and Teva, among others.
*Correction, 3/30/23: An earlier version of this article misstated the name of the company that markets Reyvow.
Headache treatment before the early 1990s was marked by decades of improvisation with mostly unapproved agents, followed by an explosion of scientific interest and new treatments developed specifically for migraine.
But this is largely thanks to the sea change that occurred 30 years ago.
In an interview, Alan M. Rapoport, MD, editor-in-chief of Neurology Reviews, past president of the International Headache Society and clinical professor of neurology at UCLA’s David Geffen School of Medicine in Los Angeles, recalled what it was like to treat patients before and after triptan medications came onto the market.
After the first of these anti-migraine agents, sumatriptan, was approved by the Food and Drug Administration in late December 1992, headache specialists found themselves with a powerful, approved treatment that validated their commitment to solving the disorder, and helped put to rest a persistent but mistaken notion that migraine was a psychiatric condition affecting young women.
But in the 1970s and 1980s, “there wasn’t great science explaining the pathophysiology of common primary headaches like tension-type headache, cluster headache, and migraine,” Dr. Rapoport recalled. “There is often comorbid depression and anxiety with migraine, and sometimes more serious psychiatric disease, but it doesn’t mean migraine is caused by psychological issues. Now we see it clearly as a disease of the brain, but it took years of investigation to prove that.”
The early years
Dr. Rapoport’s journey with headache began in 1972, when he joined a private neurology practice in Stamford and Greenwich, Conn. Neurologists were frowned upon then for having too much interest in headache, he said. There was poor remuneration for doctors treating headache patients, who were hard to properly diagnose and effectively care for. Few medications could effectively stop a migraine attack or reliably reduce the frequency of headaches or the disability they caused.
On weekends Dr. Rapoport covered emergency departments and ICUs at three hospitals, where standard treatment for a migraine attack was injectable opiates. Not only did this treatment aggravate nausea, a common migraine symptom, “but it did not stop the migraine process.” Once the pain relief wore off, patients woke up with the same headache, Dr. Rapoport recalled. “The other drug that was available was ergotamine tartrate” – a fungal alkaloid used since medieval times to treat headache – “given sublingually. It helped the headache slightly but increased the nausea. DHE, or dihydroergotamine, was available only by injection and not used very much.”
DHE, a semi-synthetic molecule based on ergotamine, had FDA approval for migraine, but was complicated to administer. Like the opioids, it provoked vomiting when given intravenously, in patients already suffering migraine-induced nausea. But Dr. Rapoport, along with some of his colleagues, felt that there was a role for DHE for the most severe subtypes of patients, those with long histories of frequent migraines.
“We put people in the hospital and we gave them intravenous DHE. Eventually I got the idea to give it intramuscularly or subcutaneously in the emergency room or my office. When you give it that way, it doesn’t work as quickly but has fewer side effects.” Dr. Rapoport designed a cocktail by coadministering promethazine for nausea, and eventually added a steroid, dexamethasone. The triple shots worked on most patients experiencing severe daily or near-daily migraine attacks, Dr. Rapoport saw, and he began administering the drug combination at The New England Center for Headache in Stamford and Greenwich, Conn., which he opened with Dr. Fred D. Sheftell in 1979.
“The triple shots really worked,” Dr. Rapoport recalled. “There was no need to keep patients in the office or emergency room for intravenous therapy. The patients never called to complain or came back the next day,” he said, as often occurred with opioid treatment.
Dr. Rapoport had learned early in his residency, in the late 1960s, from Dr. David R. Coddon, a neurologist at Mount Sinai hospital in New York, that a tricyclic antidepressant, imipramine, could be helpful in some patients with frequent migraine attacks. As evidence trickled in that other antidepressants, beta-blockers, and antiepileptic drugs might have preventive properties, Dr. Rapoport and others prescribed them for certain patients. But of all the drugs in the headache specialists’ repertoire, few were approved for either treatment or prevention. “And this continued until the triptans,” Dr. Rapoport said.
The triptan era
Sumatriptan was developed by Glaxo for the acute treatment of migraine. The medication, first available only as self-administered subcutaneous injections, was originally designed to bind to vascular serotonin receptors to allow selective constriction of cranial vessels that dilate, causing pain, during a migraine attack. (Years later it was discovered that triptans also worked as anti-inflammatory agents that decreased the release of the neurotransmitter calcitonin gene-related peptide, or CGRP.)
Triptans “changed the world for migraine patients and for me,” Dr. Rapoport said. “I could now prescribe a medication that people could take at home to decrease or stop the migraine process in an hour or two.” The success of the triptans prompted pharmaceutical companies to search for new, more effective ways to treat migraine attacks, with better tolerability.
Seven different triptans were developed, some as injections or tablets and others as nasal sprays. “If one triptan didn’t work, we’d give a second and rarely a third,” Dr. Rapoport said. “We learned that if oral triptans did not work, the most likely issue was that it was not rapidly absorbed from the small intestine, as migraine patients have nausea, poor GI absorption, and slow transit times. This prompted the greater use of injections and nasal sprays.” Headache specialists began combining triptan treatment with nonsteroidal anti-inflammatory drugs, offering further relief for the acute care of migraine.
Medication overuse headache
The years between 1993 and 2000, which saw all the current triptan drugs come onto the market, was an exhilarating one for headache specialists. But even those who were thrilled by the possibilities of the triptans, like Dr. Rapoport, soon came to recognize their limitations, in terms of side effects and poor tolerability for some patients.
Specialists also noticed something unsettling about the triptans: that patients’ headaches seemed to recur within a day, or occur more frequently over time, with higher medication use.
Medication overuse headache (MOH) was known to occur when patients treated migraine too often with acute care medications, especially over-the-counter analgesics and prescription opioids and barbiturates. Dr. Rapoport began warning at conferences and in seminars that MOH seemed to occur with the triptans as well. “In the beginning other doctors didn’t think the triptans could cause MOH, but I observed that patients who were taking triptans daily or almost daily were having increased headache frequency and the triptans stopped being effective. If they didn’t take the drug they were overusing, they were going to get much worse, almost like a withdrawal.”
Today, all seven triptans are now generic, and they remain a mainstay of migraine treatment: “Almost all of my patients are using, or have used a triptan,” Dr. Rapoport said. Yet researchers came to recognize the need for treatments targeting different pathways, both for prevention and acute care.
The next revolution: CGRP and gepants
Studies in the early 2000s began to show a link between the release of one ubiquitous nervous system neurotransmitter, calcitonin gene-related peptide, or CGRP, and migraine. They also noticed that blocking meningeal inflammation could lead to improvement in headache. Two new drug classes emerged from this science: monoclonal antibodies against CGRP or its receptor that had to be given by injection, and oral CGRP receptor blockers that could be used both as a preventive or as an acute care medication.
In 2018 the first monoclonal antibody against the CGRP receptor, erenumab (Aimovig, marketed by Amgen), delivered by injection, was approved for migraine prevention. Three others followed, most given by autoinjector, and one by IV infusion in office or hospital settings. “Those drugs are great,” Dr. Rapoport said. “You take one shot a month or every 3 months, and your headaches drop by 50% or more with very few side effects. Some patients actually see their migraines disappear.”
The following year ubrogepant (Ubrelvy, marketed by AbbVie), the first of a novel class of oral CGRP receptor blockers known as “gepants,” was approved to treat acute migraine. The FDA soon approved another gepant, rimegepant (Nurtec, marketed by Pfizer), which received indications both for prevention and for stopping a migraine attack acutely.
Both classes of therapies – the antibodies and the gepants – are far costlier than the triptans, which are all generic, and may not be needed for every migraine patient. With the gepants, for example, insurers may restrict use to people who have not responded to triptans or for whom triptans are contraindicated or cause too many adverse events. But the CGRP-targeted therapies as a whole “have been every bit as revolutionary” as the triptans, Dr. Rapoport said. The treatments work quickly to resolve headache and disability and get the patient functioning within an hour or two, and there are fewer side effects.
In a review article published in CNS Drugs in 2021, Dr. Rapoport and his colleagues reported that the anti-CGRP treatment with gepants did not appear linked to medication overuse headache, as virtually all previous acute care medication classes did, and could be used in patients who had previously reported MOH. “I am confident that over the next few years, more people will be using them as insurance coverage will improve for patients living with migraine,” he said.
Headache treatment today
Migraine specialists and patients now have a staggering range of therapeutic options. Approved treatments now include prevention of migraine with onabotulinumtoxinA (Botox, marketed by the Allergan division of AbbVie) injections, which work alone and with other medicines; acute care treatment with ditans like lasmiditan (Reyvow, marketed by Lilly*), a category of acute care medicines that work like triptans but target different serotonin receptors. Five devices have been cleared for migraine and other types of headache by the FDA. These work alone or along with medication and can be used acutely or preventively. The devices “should be used more,” Dr. Rapoport said, but are not yet well covered by insurance.
Thirty years after the triptans, scientists and researchers continue to explore the pathophysiology of headache disorders, finding new pathways and identifying new potential targets.
“There are many parts of the brain and brain stem that are involved, as well as the thalamus and hypothalamus,” Dr. Rapoport said. “It’s interesting that the newer medications, and some of the older ones, work in the peripheral nervous system, outside the brain stem in the trigeminovascular system, to modulate the central nervous system. We also know that the CGRP system is involved with cellular second-order messengers. Stimulating and blocking this chain of reactions with newer drugs may become treatments in the future.”
Recent research has focused on a blood vessel dilating neurotransmitter, pituitary adenylate-cyclase-activating polypeptide, or PACAP-38, as a potential therapeutic target. Psychedelic medications such as psilocybin, strong pain medications such as ketamine, and even cannabinoids such as marijuana have all been investigated in migraine. Biofeedback therapies, mindfulness, and other behavioral interventions also have proved effective.
“I expect the next 2-5 years to bring us many important clinical trials on new types of pharmacological treatments,” Dr. Rapoport said. “This is a wonderful time to be a doctor or nurse treating patients living with migraine. When I started out treating headache, 51 years ago, we had only ergotamine tartrate. Today we have so many therapies and combinations of therapies that I hardly know where to start.”
Dr. Rapoport has served as a consultant to or speaker for AbbVie, Amgen, Biohaven, Cala Health, Lundbeck, Satsuma, and Teva, among others.
*Correction, 3/30/23: An earlier version of this article misstated the name of the company that markets Reyvow.
Headache treatment before the early 1990s was marked by decades of improvisation with mostly unapproved agents, followed by an explosion of scientific interest and new treatments developed specifically for migraine.
But this is largely thanks to the sea change that occurred 30 years ago.
In an interview, Alan M. Rapoport, MD, editor-in-chief of Neurology Reviews, past president of the International Headache Society and clinical professor of neurology at UCLA’s David Geffen School of Medicine in Los Angeles, recalled what it was like to treat patients before and after triptan medications came onto the market.
After the first of these anti-migraine agents, sumatriptan, was approved by the Food and Drug Administration in late December 1992, headache specialists found themselves with a powerful, approved treatment that validated their commitment to solving the disorder, and helped put to rest a persistent but mistaken notion that migraine was a psychiatric condition affecting young women.
But in the 1970s and 1980s, “there wasn’t great science explaining the pathophysiology of common primary headaches like tension-type headache, cluster headache, and migraine,” Dr. Rapoport recalled. “There is often comorbid depression and anxiety with migraine, and sometimes more serious psychiatric disease, but it doesn’t mean migraine is caused by psychological issues. Now we see it clearly as a disease of the brain, but it took years of investigation to prove that.”
The early years
Dr. Rapoport’s journey with headache began in 1972, when he joined a private neurology practice in Stamford and Greenwich, Conn. Neurologists were frowned upon then for having too much interest in headache, he said. There was poor remuneration for doctors treating headache patients, who were hard to properly diagnose and effectively care for. Few medications could effectively stop a migraine attack or reliably reduce the frequency of headaches or the disability they caused.
On weekends Dr. Rapoport covered emergency departments and ICUs at three hospitals, where standard treatment for a migraine attack was injectable opiates. Not only did this treatment aggravate nausea, a common migraine symptom, “but it did not stop the migraine process.” Once the pain relief wore off, patients woke up with the same headache, Dr. Rapoport recalled. “The other drug that was available was ergotamine tartrate” – a fungal alkaloid used since medieval times to treat headache – “given sublingually. It helped the headache slightly but increased the nausea. DHE, or dihydroergotamine, was available only by injection and not used very much.”
DHE, a semi-synthetic molecule based on ergotamine, had FDA approval for migraine, but was complicated to administer. Like the opioids, it provoked vomiting when given intravenously, in patients already suffering migraine-induced nausea. But Dr. Rapoport, along with some of his colleagues, felt that there was a role for DHE for the most severe subtypes of patients, those with long histories of frequent migraines.
“We put people in the hospital and we gave them intravenous DHE. Eventually I got the idea to give it intramuscularly or subcutaneously in the emergency room or my office. When you give it that way, it doesn’t work as quickly but has fewer side effects.” Dr. Rapoport designed a cocktail by coadministering promethazine for nausea, and eventually added a steroid, dexamethasone. The triple shots worked on most patients experiencing severe daily or near-daily migraine attacks, Dr. Rapoport saw, and he began administering the drug combination at The New England Center for Headache in Stamford and Greenwich, Conn., which he opened with Dr. Fred D. Sheftell in 1979.
“The triple shots really worked,” Dr. Rapoport recalled. “There was no need to keep patients in the office or emergency room for intravenous therapy. The patients never called to complain or came back the next day,” he said, as often occurred with opioid treatment.
Dr. Rapoport had learned early in his residency, in the late 1960s, from Dr. David R. Coddon, a neurologist at Mount Sinai hospital in New York, that a tricyclic antidepressant, imipramine, could be helpful in some patients with frequent migraine attacks. As evidence trickled in that other antidepressants, beta-blockers, and antiepileptic drugs might have preventive properties, Dr. Rapoport and others prescribed them for certain patients. But of all the drugs in the headache specialists’ repertoire, few were approved for either treatment or prevention. “And this continued until the triptans,” Dr. Rapoport said.
The triptan era
Sumatriptan was developed by Glaxo for the acute treatment of migraine. The medication, first available only as self-administered subcutaneous injections, was originally designed to bind to vascular serotonin receptors to allow selective constriction of cranial vessels that dilate, causing pain, during a migraine attack. (Years later it was discovered that triptans also worked as anti-inflammatory agents that decreased the release of the neurotransmitter calcitonin gene-related peptide, or CGRP.)
Triptans “changed the world for migraine patients and for me,” Dr. Rapoport said. “I could now prescribe a medication that people could take at home to decrease or stop the migraine process in an hour or two.” The success of the triptans prompted pharmaceutical companies to search for new, more effective ways to treat migraine attacks, with better tolerability.
Seven different triptans were developed, some as injections or tablets and others as nasal sprays. “If one triptan didn’t work, we’d give a second and rarely a third,” Dr. Rapoport said. “We learned that if oral triptans did not work, the most likely issue was that it was not rapidly absorbed from the small intestine, as migraine patients have nausea, poor GI absorption, and slow transit times. This prompted the greater use of injections and nasal sprays.” Headache specialists began combining triptan treatment with nonsteroidal anti-inflammatory drugs, offering further relief for the acute care of migraine.
Medication overuse headache
The years between 1993 and 2000, which saw all the current triptan drugs come onto the market, was an exhilarating one for headache specialists. But even those who were thrilled by the possibilities of the triptans, like Dr. Rapoport, soon came to recognize their limitations, in terms of side effects and poor tolerability for some patients.
Specialists also noticed something unsettling about the triptans: that patients’ headaches seemed to recur within a day, or occur more frequently over time, with higher medication use.
Medication overuse headache (MOH) was known to occur when patients treated migraine too often with acute care medications, especially over-the-counter analgesics and prescription opioids and barbiturates. Dr. Rapoport began warning at conferences and in seminars that MOH seemed to occur with the triptans as well. “In the beginning other doctors didn’t think the triptans could cause MOH, but I observed that patients who were taking triptans daily or almost daily were having increased headache frequency and the triptans stopped being effective. If they didn’t take the drug they were overusing, they were going to get much worse, almost like a withdrawal.”
Today, all seven triptans are now generic, and they remain a mainstay of migraine treatment: “Almost all of my patients are using, or have used a triptan,” Dr. Rapoport said. Yet researchers came to recognize the need for treatments targeting different pathways, both for prevention and acute care.
The next revolution: CGRP and gepants
Studies in the early 2000s began to show a link between the release of one ubiquitous nervous system neurotransmitter, calcitonin gene-related peptide, or CGRP, and migraine. They also noticed that blocking meningeal inflammation could lead to improvement in headache. Two new drug classes emerged from this science: monoclonal antibodies against CGRP or its receptor that had to be given by injection, and oral CGRP receptor blockers that could be used both as a preventive or as an acute care medication.
In 2018 the first monoclonal antibody against the CGRP receptor, erenumab (Aimovig, marketed by Amgen), delivered by injection, was approved for migraine prevention. Three others followed, most given by autoinjector, and one by IV infusion in office or hospital settings. “Those drugs are great,” Dr. Rapoport said. “You take one shot a month or every 3 months, and your headaches drop by 50% or more with very few side effects. Some patients actually see their migraines disappear.”
The following year ubrogepant (Ubrelvy, marketed by AbbVie), the first of a novel class of oral CGRP receptor blockers known as “gepants,” was approved to treat acute migraine. The FDA soon approved another gepant, rimegepant (Nurtec, marketed by Pfizer), which received indications both for prevention and for stopping a migraine attack acutely.
Both classes of therapies – the antibodies and the gepants – are far costlier than the triptans, which are all generic, and may not be needed for every migraine patient. With the gepants, for example, insurers may restrict use to people who have not responded to triptans or for whom triptans are contraindicated or cause too many adverse events. But the CGRP-targeted therapies as a whole “have been every bit as revolutionary” as the triptans, Dr. Rapoport said. The treatments work quickly to resolve headache and disability and get the patient functioning within an hour or two, and there are fewer side effects.
In a review article published in CNS Drugs in 2021, Dr. Rapoport and his colleagues reported that the anti-CGRP treatment with gepants did not appear linked to medication overuse headache, as virtually all previous acute care medication classes did, and could be used in patients who had previously reported MOH. “I am confident that over the next few years, more people will be using them as insurance coverage will improve for patients living with migraine,” he said.
Headache treatment today
Migraine specialists and patients now have a staggering range of therapeutic options. Approved treatments now include prevention of migraine with onabotulinumtoxinA (Botox, marketed by the Allergan division of AbbVie) injections, which work alone and with other medicines; acute care treatment with ditans like lasmiditan (Reyvow, marketed by Lilly*), a category of acute care medicines that work like triptans but target different serotonin receptors. Five devices have been cleared for migraine and other types of headache by the FDA. These work alone or along with medication and can be used acutely or preventively. The devices “should be used more,” Dr. Rapoport said, but are not yet well covered by insurance.
Thirty years after the triptans, scientists and researchers continue to explore the pathophysiology of headache disorders, finding new pathways and identifying new potential targets.
“There are many parts of the brain and brain stem that are involved, as well as the thalamus and hypothalamus,” Dr. Rapoport said. “It’s interesting that the newer medications, and some of the older ones, work in the peripheral nervous system, outside the brain stem in the trigeminovascular system, to modulate the central nervous system. We also know that the CGRP system is involved with cellular second-order messengers. Stimulating and blocking this chain of reactions with newer drugs may become treatments in the future.”
Recent research has focused on a blood vessel dilating neurotransmitter, pituitary adenylate-cyclase-activating polypeptide, or PACAP-38, as a potential therapeutic target. Psychedelic medications such as psilocybin, strong pain medications such as ketamine, and even cannabinoids such as marijuana have all been investigated in migraine. Biofeedback therapies, mindfulness, and other behavioral interventions also have proved effective.
“I expect the next 2-5 years to bring us many important clinical trials on new types of pharmacological treatments,” Dr. Rapoport said. “This is a wonderful time to be a doctor or nurse treating patients living with migraine. When I started out treating headache, 51 years ago, we had only ergotamine tartrate. Today we have so many therapies and combinations of therapies that I hardly know where to start.”
Dr. Rapoport has served as a consultant to or speaker for AbbVie, Amgen, Biohaven, Cala Health, Lundbeck, Satsuma, and Teva, among others.
*Correction, 3/30/23: An earlier version of this article misstated the name of the company that markets Reyvow.
JCOM: 30 Years of Advancing Quality Improvement and Innovation in Care Delivery
This year marks the publication of the 30th volume of the Journal of Clinical Outcomes Management (JCOM). As we celebrate JCOM’s 30th year, we look forward to the future and continuing the journey to inform quality improvement leaders and practitioners about advances in the field and share experiences. The path forward on this journey involves collaboration across stakeholders, the application of innovative improvement methods, and a commitment to achieving health equity. Health care quality improvement plans must prioritize patient-centered care, promote evidence-based practices and continuous learning, and establish clear metrics to measure progress and success. Furthermore, engagement with patients and communities must be at the forefront of any quality improvement plan, as their perspectives and experiences are essential to understanding and addressing the root causes of disparities in health care delivery. Additionally, effective communication and coordination among health care providers, administrators, policymakers, and other stakeholders are crucial to achieving sustainable improvements in health care quality.
JCOM’s mission is to serve as a platform for sharing knowledge, experiences, and best practices to improve patient outcomes and promote health equity. The vision encompasses a world where all individuals have access to high-quality, patient-centered health care that is free of disparities and achieves optimal health outcomes. JCOM’s strategy is to publish articles that showcase innovative quality improvement initiatives, share evidence-based practices and research findings, highlight successful collaborations, and provide practical guidance for health care professionals to implement quality improvement initiatives in their organizations.
We believe that by sharing these insights and experiences, we can accelerate progress toward achieving equitable and high-quality health care for all individuals and communities, regardless of their socioeconomic status, race/ethnicity, gender identity, or any other factor that may impact their access to care and health outcomes. We continue to welcome submissions from all health care professionals, researchers, and other stakeholders involved in quality improvement initiatives. Together, we can work toward a future where every individual has access to the highest quality of health care and experiences equitable health outcomes.
A comprehensive and collaborative approach to health care quality improvement, which is led by a peer review process and scientific publication of the progress, is a necessary part of ensuring that all patients receive high-quality care that is equitable and patient-centered. The future of health care quality will require further research and scholarly work in the areas of training and development, data infrastructure and analytics, as well as technology-enabled solutions that support continuous improvement and innovation. Health care organizations can build a culture of quality improvement that drives meaningful progress toward achieving health equity and improving health care delivery for all by sharing the output from their research.
Thank you for joining us in this mission to improve health care quality, promote optimal health care delivery methods, and create a world where health care is not only accessible, but also equitable and of the highest standards. Let us continue to work toward building a health care system that prioritizes patient-centered care. Together, we can make a difference and ensure that every individual receives the care they need and deserve.
Corresponding author: Ebrahim Barkoudah, MD, MPH; [email protected]
This year marks the publication of the 30th volume of the Journal of Clinical Outcomes Management (JCOM). As we celebrate JCOM’s 30th year, we look forward to the future and continuing the journey to inform quality improvement leaders and practitioners about advances in the field and share experiences. The path forward on this journey involves collaboration across stakeholders, the application of innovative improvement methods, and a commitment to achieving health equity. Health care quality improvement plans must prioritize patient-centered care, promote evidence-based practices and continuous learning, and establish clear metrics to measure progress and success. Furthermore, engagement with patients and communities must be at the forefront of any quality improvement plan, as their perspectives and experiences are essential to understanding and addressing the root causes of disparities in health care delivery. Additionally, effective communication and coordination among health care providers, administrators, policymakers, and other stakeholders are crucial to achieving sustainable improvements in health care quality.
JCOM’s mission is to serve as a platform for sharing knowledge, experiences, and best practices to improve patient outcomes and promote health equity. The vision encompasses a world where all individuals have access to high-quality, patient-centered health care that is free of disparities and achieves optimal health outcomes. JCOM’s strategy is to publish articles that showcase innovative quality improvement initiatives, share evidence-based practices and research findings, highlight successful collaborations, and provide practical guidance for health care professionals to implement quality improvement initiatives in their organizations.
We believe that by sharing these insights and experiences, we can accelerate progress toward achieving equitable and high-quality health care for all individuals and communities, regardless of their socioeconomic status, race/ethnicity, gender identity, or any other factor that may impact their access to care and health outcomes. We continue to welcome submissions from all health care professionals, researchers, and other stakeholders involved in quality improvement initiatives. Together, we can work toward a future where every individual has access to the highest quality of health care and experiences equitable health outcomes.
A comprehensive and collaborative approach to health care quality improvement, which is led by a peer review process and scientific publication of the progress, is a necessary part of ensuring that all patients receive high-quality care that is equitable and patient-centered. The future of health care quality will require further research and scholarly work in the areas of training and development, data infrastructure and analytics, as well as technology-enabled solutions that support continuous improvement and innovation. Health care organizations can build a culture of quality improvement that drives meaningful progress toward achieving health equity and improving health care delivery for all by sharing the output from their research.
Thank you for joining us in this mission to improve health care quality, promote optimal health care delivery methods, and create a world where health care is not only accessible, but also equitable and of the highest standards. Let us continue to work toward building a health care system that prioritizes patient-centered care. Together, we can make a difference and ensure that every individual receives the care they need and deserve.
Corresponding author: Ebrahim Barkoudah, MD, MPH; [email protected]
This year marks the publication of the 30th volume of the Journal of Clinical Outcomes Management (JCOM). As we celebrate JCOM’s 30th year, we look forward to the future and continuing the journey to inform quality improvement leaders and practitioners about advances in the field and share experiences. The path forward on this journey involves collaboration across stakeholders, the application of innovative improvement methods, and a commitment to achieving health equity. Health care quality improvement plans must prioritize patient-centered care, promote evidence-based practices and continuous learning, and establish clear metrics to measure progress and success. Furthermore, engagement with patients and communities must be at the forefront of any quality improvement plan, as their perspectives and experiences are essential to understanding and addressing the root causes of disparities in health care delivery. Additionally, effective communication and coordination among health care providers, administrators, policymakers, and other stakeholders are crucial to achieving sustainable improvements in health care quality.
JCOM’s mission is to serve as a platform for sharing knowledge, experiences, and best practices to improve patient outcomes and promote health equity. The vision encompasses a world where all individuals have access to high-quality, patient-centered health care that is free of disparities and achieves optimal health outcomes. JCOM’s strategy is to publish articles that showcase innovative quality improvement initiatives, share evidence-based practices and research findings, highlight successful collaborations, and provide practical guidance for health care professionals to implement quality improvement initiatives in their organizations.
We believe that by sharing these insights and experiences, we can accelerate progress toward achieving equitable and high-quality health care for all individuals and communities, regardless of their socioeconomic status, race/ethnicity, gender identity, or any other factor that may impact their access to care and health outcomes. We continue to welcome submissions from all health care professionals, researchers, and other stakeholders involved in quality improvement initiatives. Together, we can work toward a future where every individual has access to the highest quality of health care and experiences equitable health outcomes.
A comprehensive and collaborative approach to health care quality improvement, which is led by a peer review process and scientific publication of the progress, is a necessary part of ensuring that all patients receive high-quality care that is equitable and patient-centered. The future of health care quality will require further research and scholarly work in the areas of training and development, data infrastructure and analytics, as well as technology-enabled solutions that support continuous improvement and innovation. Health care organizations can build a culture of quality improvement that drives meaningful progress toward achieving health equity and improving health care delivery for all by sharing the output from their research.
Thank you for joining us in this mission to improve health care quality, promote optimal health care delivery methods, and create a world where health care is not only accessible, but also equitable and of the highest standards. Let us continue to work toward building a health care system that prioritizes patient-centered care. Together, we can make a difference and ensure that every individual receives the care they need and deserve.
Corresponding author: Ebrahim Barkoudah, MD, MPH; [email protected]
Celebrity death finally solved – with locks of hair
This transcript has been edited for clarity.
I’m going to open this week with a case.
A 56-year-old musician presents with diffuse abdominal pain, cramping, and jaundice. His medical history is notable for years of diffuse abdominal complaints, characterized by disabling bouts of diarrhea.
In addition to the jaundice, this acute illness was accompanied by fever as well as diffuse edema and ascites. The patient underwent several abdominal paracenteses to drain excess fluid. One consulting physician administered alcohol to relieve pain, to little avail.
The patient succumbed to his illness. An autopsy showed diffuse liver injury, as well as papillary necrosis of the kidneys. Notably, the nerves of his auditory canal were noted to be thickened, along with the bony part of the skull, consistent with Paget disease of the bone and explaining, potentially, why the talented musician had gone deaf at such a young age.
An interesting note on social history: The patient had apparently developed some feelings for the niece of that doctor who prescribed alcohol. Her name was Therese, perhaps mistranscribed as Elise, and it seems that he may have written this song for her.
We’re talking about this paper in Current Biology, by Tristan Begg and colleagues, which gives us a look into the very genome of what some would argue is the world’s greatest composer.
The ability to extract DNA from older specimens has transformed the fields of anthropology, archaeology, and history, and now, perhaps, musicology as well.
The researchers identified eight locks of hair in private and public collections, all attributed to the maestro.
Four of the samples had an intact chain of custody from the time the hair was cut. DNA sequencing on these four and an additional one of the eight locks came from the same individual, a male of European heritage.
The three locks with less documentation came from three other unrelated individuals. Interestingly, analysis of one of those hair samples – the so-called Hiller Lock – had shown high levels of lead, leading historians to speculate that lead poisoning could account for some of Beethoven’s symptoms.
DNA analysis of that hair reveals it to have come from a woman likely of North African, Middle Eastern, or Jewish ancestry. We can no longer presume that plumbism was involved in Beethoven’s death. Beethoven’s ancestry turns out to be less exotic and maps quite well to ethnic German populations today.
In fact, there are van Beethovens alive as we speak, primarily in Belgium. Genealogic records suggest that these van Beethovens share a common ancestor with the virtuoso composer, a man by the name of Aert van Beethoven.
But the DNA reveals a scandal.
The Y-chromosome that Beethoven inherited was not Aert van Beethoven’s. Questions of Beethoven’s paternity have been raised before, but this evidence strongly suggests an extramarital paternity event, at least in the generations preceding his birth. That’s right – Beethoven may not have been a Beethoven.
With five locks now essentially certain to have come from Beethoven himself, the authors could use DNA analysis to try to explain three significant health problems he experienced throughout his life and death: his hearing loss, his terrible gastrointestinal issues, and his liver failure.
Let’s start with the most disappointing results, explanations for his hearing loss. No genetic cause was forthcoming, though the authors note that they have little to go on in regard to the genetic risk for otosclerosis, to which his hearing loss has often been attributed. Lead poisoning is, of course, possible here, though this report focuses only on genetics – there was no testing for lead – and as I mentioned, the lock that was strongly lead-positive in prior studies is almost certainly inauthentic.
What about his lifelong GI complaints? Some have suggested celiac disease or lactose intolerance as explanations. These can essentially be ruled out by the genetic analysis, which shows no risk alleles for celiac disease and the presence of the lactase-persistence gene which confers the ability to metabolize lactose throughout one’s life. IBS is harder to assess genetically, but for what it’s worth, he scored quite low on a polygenic risk score for the condition, in just the 9th percentile of risk. We should probably be looking elsewhere to explain the GI distress.
The genetic information bore much more fruit in regard to his liver disease. Remember that Beethoven’s autopsy showed cirrhosis. His polygenic risk score for liver cirrhosis puts him in the 96th percentile of risk. He was also heterozygous for two variants that can cause hereditary hemochromatosis. The risk for cirrhosis among those with these variants is increased by the use of alcohol. And historical accounts are quite clear that Beethoven consumed more than his share.
But it wasn’t just Beethoven’s DNA in these hair follicles. Analysis of a follicle from later in his life revealed the unmistakable presence of hepatitis B virus. Endemic in Europe at the time, this was a common cause of liver failure and is likely to have contributed to, if not directly caused, Beethoven’s demise.
It’s hard to read these results and not marvel at the fact that, two centuries after his death, our fascination with Beethoven has led us to probe every corner of his life – his letters, his writings, his medical records, and now his very DNA. What are we actually looking for? Is it relevant to us today what caused his hearing loss? His stomach troubles? Even his death? Will it help any patients in the future? I propose that what we are actually trying to understand is something ineffable: Genius of magnitude that is rarely seen in one or many lifetimes. And our scientific tools, as sharp as they may have become, are still far too blunt to probe the depths of that transcendence.
In any case, friends, no more of these sounds. Let us sing more cheerful songs, more full of joy.
For Medscape, I’m Perry Wilson.
Dr. Wilson is associate professor, department of medicine, and director, Clinical and Translational Research Accelerator, at Yale University, New Haven, Conn. He reported no conflicts of interest.
A version of this article first appeared on Medscape.com.
This transcript has been edited for clarity.
I’m going to open this week with a case.
A 56-year-old musician presents with diffuse abdominal pain, cramping, and jaundice. His medical history is notable for years of diffuse abdominal complaints, characterized by disabling bouts of diarrhea.
In addition to the jaundice, this acute illness was accompanied by fever as well as diffuse edema and ascites. The patient underwent several abdominal paracenteses to drain excess fluid. One consulting physician administered alcohol to relieve pain, to little avail.
The patient succumbed to his illness. An autopsy showed diffuse liver injury, as well as papillary necrosis of the kidneys. Notably, the nerves of his auditory canal were noted to be thickened, along with the bony part of the skull, consistent with Paget disease of the bone and explaining, potentially, why the talented musician had gone deaf at such a young age.
An interesting note on social history: The patient had apparently developed some feelings for the niece of that doctor who prescribed alcohol. Her name was Therese, perhaps mistranscribed as Elise, and it seems that he may have written this song for her.
We’re talking about this paper in Current Biology, by Tristan Begg and colleagues, which gives us a look into the very genome of what some would argue is the world’s greatest composer.
The ability to extract DNA from older specimens has transformed the fields of anthropology, archaeology, and history, and now, perhaps, musicology as well.
The researchers identified eight locks of hair in private and public collections, all attributed to the maestro.
Four of the samples had an intact chain of custody from the time the hair was cut. DNA sequencing on these four and an additional one of the eight locks came from the same individual, a male of European heritage.
The three locks with less documentation came from three other unrelated individuals. Interestingly, analysis of one of those hair samples – the so-called Hiller Lock – had shown high levels of lead, leading historians to speculate that lead poisoning could account for some of Beethoven’s symptoms.
DNA analysis of that hair reveals it to have come from a woman likely of North African, Middle Eastern, or Jewish ancestry. We can no longer presume that plumbism was involved in Beethoven’s death. Beethoven’s ancestry turns out to be less exotic and maps quite well to ethnic German populations today.
In fact, there are van Beethovens alive as we speak, primarily in Belgium. Genealogic records suggest that these van Beethovens share a common ancestor with the virtuoso composer, a man by the name of Aert van Beethoven.
But the DNA reveals a scandal.
The Y-chromosome that Beethoven inherited was not Aert van Beethoven’s. Questions of Beethoven’s paternity have been raised before, but this evidence strongly suggests an extramarital paternity event, at least in the generations preceding his birth. That’s right – Beethoven may not have been a Beethoven.
With five locks now essentially certain to have come from Beethoven himself, the authors could use DNA analysis to try to explain three significant health problems he experienced throughout his life and death: his hearing loss, his terrible gastrointestinal issues, and his liver failure.
Let’s start with the most disappointing results, explanations for his hearing loss. No genetic cause was forthcoming, though the authors note that they have little to go on in regard to the genetic risk for otosclerosis, to which his hearing loss has often been attributed. Lead poisoning is, of course, possible here, though this report focuses only on genetics – there was no testing for lead – and as I mentioned, the lock that was strongly lead-positive in prior studies is almost certainly inauthentic.
What about his lifelong GI complaints? Some have suggested celiac disease or lactose intolerance as explanations. These can essentially be ruled out by the genetic analysis, which shows no risk alleles for celiac disease and the presence of the lactase-persistence gene which confers the ability to metabolize lactose throughout one’s life. IBS is harder to assess genetically, but for what it’s worth, he scored quite low on a polygenic risk score for the condition, in just the 9th percentile of risk. We should probably be looking elsewhere to explain the GI distress.
The genetic information bore much more fruit in regard to his liver disease. Remember that Beethoven’s autopsy showed cirrhosis. His polygenic risk score for liver cirrhosis puts him in the 96th percentile of risk. He was also heterozygous for two variants that can cause hereditary hemochromatosis. The risk for cirrhosis among those with these variants is increased by the use of alcohol. And historical accounts are quite clear that Beethoven consumed more than his share.
But it wasn’t just Beethoven’s DNA in these hair follicles. Analysis of a follicle from later in his life revealed the unmistakable presence of hepatitis B virus. Endemic in Europe at the time, this was a common cause of liver failure and is likely to have contributed to, if not directly caused, Beethoven’s demise.
It’s hard to read these results and not marvel at the fact that, two centuries after his death, our fascination with Beethoven has led us to probe every corner of his life – his letters, his writings, his medical records, and now his very DNA. What are we actually looking for? Is it relevant to us today what caused his hearing loss? His stomach troubles? Even his death? Will it help any patients in the future? I propose that what we are actually trying to understand is something ineffable: Genius of magnitude that is rarely seen in one or many lifetimes. And our scientific tools, as sharp as they may have become, are still far too blunt to probe the depths of that transcendence.
In any case, friends, no more of these sounds. Let us sing more cheerful songs, more full of joy.
For Medscape, I’m Perry Wilson.
Dr. Wilson is associate professor, department of medicine, and director, Clinical and Translational Research Accelerator, at Yale University, New Haven, Conn. He reported no conflicts of interest.
A version of this article first appeared on Medscape.com.
This transcript has been edited for clarity.
I’m going to open this week with a case.
A 56-year-old musician presents with diffuse abdominal pain, cramping, and jaundice. His medical history is notable for years of diffuse abdominal complaints, characterized by disabling bouts of diarrhea.
In addition to the jaundice, this acute illness was accompanied by fever as well as diffuse edema and ascites. The patient underwent several abdominal paracenteses to drain excess fluid. One consulting physician administered alcohol to relieve pain, to little avail.
The patient succumbed to his illness. An autopsy showed diffuse liver injury, as well as papillary necrosis of the kidneys. Notably, the nerves of his auditory canal were noted to be thickened, along with the bony part of the skull, consistent with Paget disease of the bone and explaining, potentially, why the talented musician had gone deaf at such a young age.
An interesting note on social history: The patient had apparently developed some feelings for the niece of that doctor who prescribed alcohol. Her name was Therese, perhaps mistranscribed as Elise, and it seems that he may have written this song for her.
We’re talking about this paper in Current Biology, by Tristan Begg and colleagues, which gives us a look into the very genome of what some would argue is the world’s greatest composer.
The ability to extract DNA from older specimens has transformed the fields of anthropology, archaeology, and history, and now, perhaps, musicology as well.
The researchers identified eight locks of hair in private and public collections, all attributed to the maestro.
Four of the samples had an intact chain of custody from the time the hair was cut. DNA sequencing on these four and an additional one of the eight locks came from the same individual, a male of European heritage.
The three locks with less documentation came from three other unrelated individuals. Interestingly, analysis of one of those hair samples – the so-called Hiller Lock – had shown high levels of lead, leading historians to speculate that lead poisoning could account for some of Beethoven’s symptoms.
DNA analysis of that hair reveals it to have come from a woman likely of North African, Middle Eastern, or Jewish ancestry. We can no longer presume that plumbism was involved in Beethoven’s death. Beethoven’s ancestry turns out to be less exotic and maps quite well to ethnic German populations today.
In fact, there are van Beethovens alive as we speak, primarily in Belgium. Genealogic records suggest that these van Beethovens share a common ancestor with the virtuoso composer, a man by the name of Aert van Beethoven.
But the DNA reveals a scandal.
The Y-chromosome that Beethoven inherited was not Aert van Beethoven’s. Questions of Beethoven’s paternity have been raised before, but this evidence strongly suggests an extramarital paternity event, at least in the generations preceding his birth. That’s right – Beethoven may not have been a Beethoven.
With five locks now essentially certain to have come from Beethoven himself, the authors could use DNA analysis to try to explain three significant health problems he experienced throughout his life and death: his hearing loss, his terrible gastrointestinal issues, and his liver failure.
Let’s start with the most disappointing results, explanations for his hearing loss. No genetic cause was forthcoming, though the authors note that they have little to go on in regard to the genetic risk for otosclerosis, to which his hearing loss has often been attributed. Lead poisoning is, of course, possible here, though this report focuses only on genetics – there was no testing for lead – and as I mentioned, the lock that was strongly lead-positive in prior studies is almost certainly inauthentic.
What about his lifelong GI complaints? Some have suggested celiac disease or lactose intolerance as explanations. These can essentially be ruled out by the genetic analysis, which shows no risk alleles for celiac disease and the presence of the lactase-persistence gene which confers the ability to metabolize lactose throughout one’s life. IBS is harder to assess genetically, but for what it’s worth, he scored quite low on a polygenic risk score for the condition, in just the 9th percentile of risk. We should probably be looking elsewhere to explain the GI distress.
The genetic information bore much more fruit in regard to his liver disease. Remember that Beethoven’s autopsy showed cirrhosis. His polygenic risk score for liver cirrhosis puts him in the 96th percentile of risk. He was also heterozygous for two variants that can cause hereditary hemochromatosis. The risk for cirrhosis among those with these variants is increased by the use of alcohol. And historical accounts are quite clear that Beethoven consumed more than his share.
But it wasn’t just Beethoven’s DNA in these hair follicles. Analysis of a follicle from later in his life revealed the unmistakable presence of hepatitis B virus. Endemic in Europe at the time, this was a common cause of liver failure and is likely to have contributed to, if not directly caused, Beethoven’s demise.
It’s hard to read these results and not marvel at the fact that, two centuries after his death, our fascination with Beethoven has led us to probe every corner of his life – his letters, his writings, his medical records, and now his very DNA. What are we actually looking for? Is it relevant to us today what caused his hearing loss? His stomach troubles? Even his death? Will it help any patients in the future? I propose that what we are actually trying to understand is something ineffable: Genius of magnitude that is rarely seen in one or many lifetimes. And our scientific tools, as sharp as they may have become, are still far too blunt to probe the depths of that transcendence.
In any case, friends, no more of these sounds. Let us sing more cheerful songs, more full of joy.
For Medscape, I’m Perry Wilson.
Dr. Wilson is associate professor, department of medicine, and director, Clinical and Translational Research Accelerator, at Yale University, New Haven, Conn. He reported no conflicts of interest.
A version of this article first appeared on Medscape.com.
Fast, cheap ... or accurate?
A recent study on the JAMA Network found that, .
Does this surprise anyone?
One of my friends, a pharmacist, has a sign in his home office: “Fast. Accurate. Cheap. You can’t have all 3.” A true statement. I’ve also seen it at car repair places, but they’re doctors in their own way.
The problem here is that physicians are increasingly squeezed for time. If your only revenue stream is seeing patients, and your expenses are going up (and whose aren’t?) then your options are to either raise your prices or see more patients.
Of course, raising prices in medicine can’t happen for most of us. We’re all tied into insurance contracts, which themselves are pegged to Medicare, as to how much we get paid. I mean, yes, you can raise your prices, but that doesn’t matter. The insurance company will still pay a predetermined amount set years ago, in better economic times, no matter what you charge.
So the only real option for most is to see more patients. Which means less time with each one. Which, inevitably, leads to more snap judgments, inappropriate prescriptions, and mistakes.
Patients may get Fast and Cheap, but Accurate gets sidelined. This is the nature of things. If you don’t have enough time to gather and process data, then you’re less likely to reach the right answer.
There’s also the fact that sometimes it’s easier for anyone to just take the path of least resistance. The patient wants an antibiotic, and you realize it’s going to take less time to hand them a script for one than to explain why they don’t need it for what’s probably a viral infection. Not only that, but then you run the risk of their giving you a bad Yelp review (“incompetent, refused to give me antibiotics when I obviously needed them, 1 star”) and who needs that? If you’re employed by a large health care system a bad online review will get you a talking-to by some nonmedical admin from marketing, saying you’re hurting the practice’s “brand.”
Years ago the satire site The Onion had an article about a doctor who specialized in “giving a shit” - assumedly where Accurate dominates. While none of us may intentionally rush through patients or do half-assed jobs, we also have to deal with pressures of time. There never seems to be enough in a workday.
Nowhere is this more true than in primary care, where the pressures of time, overhead, and a large patient volume intersect. There are patients to see, labs to review, phone calls to return, forms to complete, meetings to attend, samples to sign for ... and probably many other things I’ve left out.
The fact that this situation exists shouldn’t surprise anyone. People talk about “burnout” and “making health care better” but that just seems to be lip service. They give you a free subscription to a meditation app, phone access to a counselor, and a mandatory early morning meeting to discuss stress reduction. Of course, these things take time away from seeing patients, which sort of defeats the whole purpose. Unless you want to do them at home – taking time away from your family, or doing the taxes, or other things you have to do besides your day job.
This is not sustainable for patients, doctors, or the health care system as a whole. But right now the situation is only getting worse, and there aren’t any easy answers.
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
A recent study on the JAMA Network found that, .
Does this surprise anyone?
One of my friends, a pharmacist, has a sign in his home office: “Fast. Accurate. Cheap. You can’t have all 3.” A true statement. I’ve also seen it at car repair places, but they’re doctors in their own way.
The problem here is that physicians are increasingly squeezed for time. If your only revenue stream is seeing patients, and your expenses are going up (and whose aren’t?) then your options are to either raise your prices or see more patients.
Of course, raising prices in medicine can’t happen for most of us. We’re all tied into insurance contracts, which themselves are pegged to Medicare, as to how much we get paid. I mean, yes, you can raise your prices, but that doesn’t matter. The insurance company will still pay a predetermined amount set years ago, in better economic times, no matter what you charge.
So the only real option for most is to see more patients. Which means less time with each one. Which, inevitably, leads to more snap judgments, inappropriate prescriptions, and mistakes.
Patients may get Fast and Cheap, but Accurate gets sidelined. This is the nature of things. If you don’t have enough time to gather and process data, then you’re less likely to reach the right answer.
There’s also the fact that sometimes it’s easier for anyone to just take the path of least resistance. The patient wants an antibiotic, and you realize it’s going to take less time to hand them a script for one than to explain why they don’t need it for what’s probably a viral infection. Not only that, but then you run the risk of their giving you a bad Yelp review (“incompetent, refused to give me antibiotics when I obviously needed them, 1 star”) and who needs that? If you’re employed by a large health care system a bad online review will get you a talking-to by some nonmedical admin from marketing, saying you’re hurting the practice’s “brand.”
Years ago the satire site The Onion had an article about a doctor who specialized in “giving a shit” - assumedly where Accurate dominates. While none of us may intentionally rush through patients or do half-assed jobs, we also have to deal with pressures of time. There never seems to be enough in a workday.
Nowhere is this more true than in primary care, where the pressures of time, overhead, and a large patient volume intersect. There are patients to see, labs to review, phone calls to return, forms to complete, meetings to attend, samples to sign for ... and probably many other things I’ve left out.
The fact that this situation exists shouldn’t surprise anyone. People talk about “burnout” and “making health care better” but that just seems to be lip service. They give you a free subscription to a meditation app, phone access to a counselor, and a mandatory early morning meeting to discuss stress reduction. Of course, these things take time away from seeing patients, which sort of defeats the whole purpose. Unless you want to do them at home – taking time away from your family, or doing the taxes, or other things you have to do besides your day job.
This is not sustainable for patients, doctors, or the health care system as a whole. But right now the situation is only getting worse, and there aren’t any easy answers.
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
A recent study on the JAMA Network found that, .
Does this surprise anyone?
One of my friends, a pharmacist, has a sign in his home office: “Fast. Accurate. Cheap. You can’t have all 3.” A true statement. I’ve also seen it at car repair places, but they’re doctors in their own way.
The problem here is that physicians are increasingly squeezed for time. If your only revenue stream is seeing patients, and your expenses are going up (and whose aren’t?) then your options are to either raise your prices or see more patients.
Of course, raising prices in medicine can’t happen for most of us. We’re all tied into insurance contracts, which themselves are pegged to Medicare, as to how much we get paid. I mean, yes, you can raise your prices, but that doesn’t matter. The insurance company will still pay a predetermined amount set years ago, in better economic times, no matter what you charge.
So the only real option for most is to see more patients. Which means less time with each one. Which, inevitably, leads to more snap judgments, inappropriate prescriptions, and mistakes.
Patients may get Fast and Cheap, but Accurate gets sidelined. This is the nature of things. If you don’t have enough time to gather and process data, then you’re less likely to reach the right answer.
There’s also the fact that sometimes it’s easier for anyone to just take the path of least resistance. The patient wants an antibiotic, and you realize it’s going to take less time to hand them a script for one than to explain why they don’t need it for what’s probably a viral infection. Not only that, but then you run the risk of their giving you a bad Yelp review (“incompetent, refused to give me antibiotics when I obviously needed them, 1 star”) and who needs that? If you’re employed by a large health care system a bad online review will get you a talking-to by some nonmedical admin from marketing, saying you’re hurting the practice’s “brand.”
Years ago the satire site The Onion had an article about a doctor who specialized in “giving a shit” - assumedly where Accurate dominates. While none of us may intentionally rush through patients or do half-assed jobs, we also have to deal with pressures of time. There never seems to be enough in a workday.
Nowhere is this more true than in primary care, where the pressures of time, overhead, and a large patient volume intersect. There are patients to see, labs to review, phone calls to return, forms to complete, meetings to attend, samples to sign for ... and probably many other things I’ve left out.
The fact that this situation exists shouldn’t surprise anyone. People talk about “burnout” and “making health care better” but that just seems to be lip service. They give you a free subscription to a meditation app, phone access to a counselor, and a mandatory early morning meeting to discuss stress reduction. Of course, these things take time away from seeing patients, which sort of defeats the whole purpose. Unless you want to do them at home – taking time away from your family, or doing the taxes, or other things you have to do besides your day job.
This is not sustainable for patients, doctors, or the health care system as a whole. But right now the situation is only getting worse, and there aren’t any easy answers.
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
COVID can mimic prostate cancer symptoms
This patient has a strong likelihood of aggressive prostate cancer, right? If that same patient also presents with severe, burning bone pain with no precipitating trauma to the area and rest and over-the-counter painkillers are not helping, you’d think, “check for metastases,” right?
That patient was me in late January 2023.
As a research scientist member of the American Urological Association, I knew enough to know I had to consult my urologist ASAP.
With the above symptoms, I’ll admit I was scared. Fortunately, if that’s the right word, I was no stranger to a rapid, dramatic spike in PSA. In 2021 I was temporarily living in a new city, and I wanted to form a relationship with a good local urologist. The urologist that I was referred to gave me a thorough consultation, including a vigorous digital rectal exam (DRE) and sent me across the street for a blood draw.
To my shock, my PSA had spiked over 2 points, to 9.9 from 7.8 a few months earlier. I freaked. Had my 3-cm tumor burst out into an aggressive cancer? Research on PubMed provided an array of studies showing what could cause PSA to suddenly rise, including a DRE performed 72 hours before the blood draw.1 A week later, my PSA was back down to its normal 7.6.
But in January 2023, I had none of those previously reported experiences that could suddenly trigger a spike in PSA, like a DRE or riding on a thin bicycle seat for a few hours before the lab visit.
The COVID effect
I went back to PubMed and found a new circumstance that could cause a surge in PSA: COVID-19. A recent study2 of 91 men with benign prostatic hypertrophy by researchers in Turkey found that PSA spiked from 0 to 5 points during the COVID infection period and up to 2 points higher 3 months after the infection had cleared. I had tested positive for COVID-19 in mid-December 2022, 4 weeks before my 9.9 PSA reading.
Using Google translate, I communicated with the team in Turkey and found out that the PSA spike can last up to 6 months.
That study helps explain why my PSA dropped over 1.5 points to 8.5 just 2 weeks after the 9.9 reading, with the expectation that it would return to its previous normal of 7.8 within 6 months of infection with SARS-CoV-2. To be safe, my urologist scheduled another PSA test in May, along with an updated multiparametric MRI, which may be followed by an in-bore MRI-guided biopsy of the 3-cm tumor if the mass has enlarged.
COVID-19 pain
What about my burning bone pain in my upper right humerus and right rotator cuff that was not precipitated by trauma or strain? A radiograph found no evidence of metastasis, thank goodness. And my research showed that several studies3 have found that COVID-19 can cause burning musculoskeletal pain, including enthesopathy, which is what I had per the radiology report. So my PSA spike and searing pain were likely consequences of the infection.
To avoid the risk for a gross misdiagnosis after a radical spike in PSA, the informed urologist should ask the patient if he has had COVID-19 in the previous 6 months. Overlooking that question could lead to the wrong diagnostic decisions about a rapid jump in PSA or unexplained bone pain.
References
1. Bossens MM et al. Eur J Cancer. 1995;31A:682-5.
2. Cinislioglu AE et al. Urology. 2022;159:16-21.
3. Ciaffi J et al. Joint Bone Spine. 2021;88:105158.
Dr. Keller is founder of the Keller Research Institute, Jacksonville, Fla. He reported serving as a research scientist for the American Urological Association, serving on the advisory board of Active Surveillance Patient’s International, and serving on the boards of numerous nonprofit organizations.
A version of this article first appeared on Medscape.com.
This patient has a strong likelihood of aggressive prostate cancer, right? If that same patient also presents with severe, burning bone pain with no precipitating trauma to the area and rest and over-the-counter painkillers are not helping, you’d think, “check for metastases,” right?
That patient was me in late January 2023.
As a research scientist member of the American Urological Association, I knew enough to know I had to consult my urologist ASAP.
With the above symptoms, I’ll admit I was scared. Fortunately, if that’s the right word, I was no stranger to a rapid, dramatic spike in PSA. In 2021 I was temporarily living in a new city, and I wanted to form a relationship with a good local urologist. The urologist that I was referred to gave me a thorough consultation, including a vigorous digital rectal exam (DRE) and sent me across the street for a blood draw.
To my shock, my PSA had spiked over 2 points, to 9.9 from 7.8 a few months earlier. I freaked. Had my 3-cm tumor burst out into an aggressive cancer? Research on PubMed provided an array of studies showing what could cause PSA to suddenly rise, including a DRE performed 72 hours before the blood draw.1 A week later, my PSA was back down to its normal 7.6.
But in January 2023, I had none of those previously reported experiences that could suddenly trigger a spike in PSA, like a DRE or riding on a thin bicycle seat for a few hours before the lab visit.
The COVID effect
I went back to PubMed and found a new circumstance that could cause a surge in PSA: COVID-19. A recent study2 of 91 men with benign prostatic hypertrophy by researchers in Turkey found that PSA spiked from 0 to 5 points during the COVID infection period and up to 2 points higher 3 months after the infection had cleared. I had tested positive for COVID-19 in mid-December 2022, 4 weeks before my 9.9 PSA reading.
Using Google translate, I communicated with the team in Turkey and found out that the PSA spike can last up to 6 months.
That study helps explain why my PSA dropped over 1.5 points to 8.5 just 2 weeks after the 9.9 reading, with the expectation that it would return to its previous normal of 7.8 within 6 months of infection with SARS-CoV-2. To be safe, my urologist scheduled another PSA test in May, along with an updated multiparametric MRI, which may be followed by an in-bore MRI-guided biopsy of the 3-cm tumor if the mass has enlarged.
COVID-19 pain
What about my burning bone pain in my upper right humerus and right rotator cuff that was not precipitated by trauma or strain? A radiograph found no evidence of metastasis, thank goodness. And my research showed that several studies3 have found that COVID-19 can cause burning musculoskeletal pain, including enthesopathy, which is what I had per the radiology report. So my PSA spike and searing pain were likely consequences of the infection.
To avoid the risk for a gross misdiagnosis after a radical spike in PSA, the informed urologist should ask the patient if he has had COVID-19 in the previous 6 months. Overlooking that question could lead to the wrong diagnostic decisions about a rapid jump in PSA or unexplained bone pain.
References
1. Bossens MM et al. Eur J Cancer. 1995;31A:682-5.
2. Cinislioglu AE et al. Urology. 2022;159:16-21.
3. Ciaffi J et al. Joint Bone Spine. 2021;88:105158.
Dr. Keller is founder of the Keller Research Institute, Jacksonville, Fla. He reported serving as a research scientist for the American Urological Association, serving on the advisory board of Active Surveillance Patient’s International, and serving on the boards of numerous nonprofit organizations.
A version of this article first appeared on Medscape.com.
This patient has a strong likelihood of aggressive prostate cancer, right? If that same patient also presents with severe, burning bone pain with no precipitating trauma to the area and rest and over-the-counter painkillers are not helping, you’d think, “check for metastases,” right?
That patient was me in late January 2023.
As a research scientist member of the American Urological Association, I knew enough to know I had to consult my urologist ASAP.
With the above symptoms, I’ll admit I was scared. Fortunately, if that’s the right word, I was no stranger to a rapid, dramatic spike in PSA. In 2021 I was temporarily living in a new city, and I wanted to form a relationship with a good local urologist. The urologist that I was referred to gave me a thorough consultation, including a vigorous digital rectal exam (DRE) and sent me across the street for a blood draw.
To my shock, my PSA had spiked over 2 points, to 9.9 from 7.8 a few months earlier. I freaked. Had my 3-cm tumor burst out into an aggressive cancer? Research on PubMed provided an array of studies showing what could cause PSA to suddenly rise, including a DRE performed 72 hours before the blood draw.1 A week later, my PSA was back down to its normal 7.6.
But in January 2023, I had none of those previously reported experiences that could suddenly trigger a spike in PSA, like a DRE or riding on a thin bicycle seat for a few hours before the lab visit.
The COVID effect
I went back to PubMed and found a new circumstance that could cause a surge in PSA: COVID-19. A recent study2 of 91 men with benign prostatic hypertrophy by researchers in Turkey found that PSA spiked from 0 to 5 points during the COVID infection period and up to 2 points higher 3 months after the infection had cleared. I had tested positive for COVID-19 in mid-December 2022, 4 weeks before my 9.9 PSA reading.
Using Google translate, I communicated with the team in Turkey and found out that the PSA spike can last up to 6 months.
That study helps explain why my PSA dropped over 1.5 points to 8.5 just 2 weeks after the 9.9 reading, with the expectation that it would return to its previous normal of 7.8 within 6 months of infection with SARS-CoV-2. To be safe, my urologist scheduled another PSA test in May, along with an updated multiparametric MRI, which may be followed by an in-bore MRI-guided biopsy of the 3-cm tumor if the mass has enlarged.
COVID-19 pain
What about my burning bone pain in my upper right humerus and right rotator cuff that was not precipitated by trauma or strain? A radiograph found no evidence of metastasis, thank goodness. And my research showed that several studies3 have found that COVID-19 can cause burning musculoskeletal pain, including enthesopathy, which is what I had per the radiology report. So my PSA spike and searing pain were likely consequences of the infection.
To avoid the risk for a gross misdiagnosis after a radical spike in PSA, the informed urologist should ask the patient if he has had COVID-19 in the previous 6 months. Overlooking that question could lead to the wrong diagnostic decisions about a rapid jump in PSA or unexplained bone pain.
References
1. Bossens MM et al. Eur J Cancer. 1995;31A:682-5.
2. Cinislioglu AE et al. Urology. 2022;159:16-21.
3. Ciaffi J et al. Joint Bone Spine. 2021;88:105158.
Dr. Keller is founder of the Keller Research Institute, Jacksonville, Fla. He reported serving as a research scientist for the American Urological Association, serving on the advisory board of Active Surveillance Patient’s International, and serving on the boards of numerous nonprofit organizations.
A version of this article first appeared on Medscape.com.