Interesting perspective, but very limited compared to actual clinical practice. Choosing over prescribing of anti-depressants ( SSRIs in particular ) is low hanging fruit, in that a large driver of this pattern is a robust marketing campaign similar to the initial enthusiasm for benzodiazepines. Ironic, in the absence if prescribed medications, people choose to self treat with alcohol, opioids, marijuana, etc.
In most clinical encounters, the disease will not resolve on its own. Untreated diabetes, hypertension, hypercholesterolemia, cancers resolve via death. The fact that treatments for disease is not perfect should not cause therapeutic nihilism , which is the distinct impression I get from this editorial.
I am aware that my opinion will be criticized for not appreciating the nuance of this article and its framing. Frankly, I find it to be one dimensional and not in any way reflective if the complexity of modern medicine and the social/ economic environment in which practice is enmeshed .
Bravo! Your depression treatment scenario fits almost every primary care scenario. Health is not achieved through a drug. A drug may or may not be a helpful tool only when combined with meaningful lifestyle changes. I believe that bioidentical hormone replacement is a valuable therapy for peri/menopause/post menopause women when used in conjunction with exercise, a whole foods ( not the store ha) diet, sleep management, etc. Many don't want to "do all the things" and they just want a pill to "fix them."
Sadly that is a perspective of the wealthy / upper middle class mindset. The “things” you promote are not easily accessible to poor, working poor and lower middle class individuals.
Fabulous piece. I’m for clinical trials all day every day. But I’ve long been fascinated and frustrated by the inherent dissonance of applying their results which merely represent average effects.
I’ve long used the example of a hypothetical blockbuster treatment with an ARR of 10% and an NNT of 10. No brainer to recommend its use. But no one patient experiences 10% less of an MI, or 10% less death; rather, 1 lucky schlub wins, while the other 9 who have listened to me have completely wasted their time (and money, and pill burden, and side effects). And I have no idea about who is the “one”, and who are the “other 9”.
This seems analogous to the issues with the “3 month follow up”. Those who improve, may have improved anyway (without therapy). And those who haven’t yet, maybe were never going to….or simply haven’t yet…and we still don’t know which is which.
This is not a call for therapeutic nihilism. We should still take the best evidence that is available, factor in the patient’s comorbidities and overall status, and understand their personal preferences, to arrive at a therapeutic decision. Your basic Sackett EBM paradigm. But this piece once again serves as a very useful reminder of the known unknowns.
Excellent article with many important insights. The function of the physician is to differentiate health from disease and to prescribe treatments to ameliorate the symptoms and/or, more rarely, cure the disease. This is often effective for a number of organic disorders ranging from congestive heart failure to hypothyroidism. There is no treatment for those disorders thought to be psychological in origin such as depression and related mood disorders. Likewise, no treatment for many disorders without a defined cause such as pre-senile dementia. But the real theater in modern medical practice today is mostly found in "preventive" medicine. As the author points out, much of this is justified by finding a couple of percentage point differences in real risk reduction over a few years in studies with variable exclusion criteria and composite end points largely driven by relatively soft components within them. Yet these types of "data" are often quoted to individual patients when they are given a specific range of "risk" for any of the common cardiovascular disorders over periods as long as ten or more years.
Much thanks for a thoughtful post. I am unsure whether I understand the gist of the discussion. My thoughts center around whether it really matters if a treatment effect rests upon biased assumptions. When considering a diagnosis of MDD or Alzheimer’s dementia, where the vagaries of human behavior are embedded in the definition no matter how rigorously it may be defined, it is inherently difficult to isolate a true treatment effect. Is this delineation important as long as the patient feels better and no major harm is identified? I am not clear on the answer.
I am wondering… it seems as if your argument asserts that, more often than not, my treatment interventions will have little and mostly limited effects, and there will be no way for me or the patient to determine or detect these. So, does this not mean we are all of us are engaged in a useless delusion of care which would best be abandoned once realized. Perhaps I should better spend my time learning to be a religious faith healer…?
The title is a bit baffling. On first glance it looks like the article was going to be about the effect of a physician's bedside manner on outcomes. It never mentions this element of care, but perhaps it suggests this indirectly. Given the very limited benefit from most prescriptions, it appears that a good physician takes up an actor-like role: He or she trots out the prescription pad, and states with gravitas and calm reassurance that this medication is 'just right for your depression'. -even while not really believing this is the case, just like the actor knows he really isn't Macbeth.
It’s even worse than this. Antidepressants are tested over very short time frames but prescribed for years or even a lifetime. Negative side effects accumulate with no benefit. A significant percentage have great difficulty discontinuing. Withdrawal symptoms from the drug are often mistaken for a relapse of depression. It’s remarkable how an educated society can be so brainwashed.
I think “minimally important difference” is used to illustrate how a study will report a treatment effect even when the magnitude of that effect is not enough to be perceived by the patient.
Biggest logic flaw of this essay is assuming each patient will only experience average treatment effect as measured by the clinical trial.
More realistically, some patients will benefit more and some will not. Non-responders will stop treatment. So actual treatment benefit on an responder may be a lot better than the average effect.
When it comes to depression, it's a bit more complicated. Classic MDD has been around since the dawn of mankind and is always associated with loss of appetite and weight loss. It is also very rare. Most people today have "atypical depression," which is associated with increased appetite and weight gain. It has only been around for about 70 years, since ultra-processed food took over our diet. In my opinion, atypical depression is caused by our modern diet and has nothing to do with MDD. I changed the name to Carbohydrate Associated Reversible Brain syndrome or CARB syndrome: https://carbsyndrome.com/
SSRI medication makes CARB syndrome worse over time, which really screws up any studies of depression.
You picked tough examples.
Interesting perspective, but very limited compared to actual clinical practice. Choosing over prescribing of anti-depressants ( SSRIs in particular ) is low hanging fruit, in that a large driver of this pattern is a robust marketing campaign similar to the initial enthusiasm for benzodiazepines. Ironic, in the absence if prescribed medications, people choose to self treat with alcohol, opioids, marijuana, etc.
In most clinical encounters, the disease will not resolve on its own. Untreated diabetes, hypertension, hypercholesterolemia, cancers resolve via death. The fact that treatments for disease is not perfect should not cause therapeutic nihilism , which is the distinct impression I get from this editorial.
I am aware that my opinion will be criticized for not appreciating the nuance of this article and its framing. Frankly, I find it to be one dimensional and not in any way reflective if the complexity of modern medicine and the social/ economic environment in which practice is enmeshed .
Bravo! Your depression treatment scenario fits almost every primary care scenario. Health is not achieved through a drug. A drug may or may not be a helpful tool only when combined with meaningful lifestyle changes. I believe that bioidentical hormone replacement is a valuable therapy for peri/menopause/post menopause women when used in conjunction with exercise, a whole foods ( not the store ha) diet, sleep management, etc. Many don't want to "do all the things" and they just want a pill to "fix them."
Sadly that is a perspective of the wealthy / upper middle class mindset. The “things” you promote are not easily accessible to poor, working poor and lower middle class individuals.
Was it Voltaire who said that the chief aim of the physician is to amuse the patient while nature cures the disease?
Fabulous piece. I’m for clinical trials all day every day. But I’ve long been fascinated and frustrated by the inherent dissonance of applying their results which merely represent average effects.
I’ve long used the example of a hypothetical blockbuster treatment with an ARR of 10% and an NNT of 10. No brainer to recommend its use. But no one patient experiences 10% less of an MI, or 10% less death; rather, 1 lucky schlub wins, while the other 9 who have listened to me have completely wasted their time (and money, and pill burden, and side effects). And I have no idea about who is the “one”, and who are the “other 9”.
This seems analogous to the issues with the “3 month follow up”. Those who improve, may have improved anyway (without therapy). And those who haven’t yet, maybe were never going to….or simply haven’t yet…and we still don’t know which is which.
This is not a call for therapeutic nihilism. We should still take the best evidence that is available, factor in the patient’s comorbidities and overall status, and understand their personal preferences, to arrive at a therapeutic decision. Your basic Sackett EBM paradigm. But this piece once again serves as a very useful reminder of the known unknowns.
Excellent article with many important insights. The function of the physician is to differentiate health from disease and to prescribe treatments to ameliorate the symptoms and/or, more rarely, cure the disease. This is often effective for a number of organic disorders ranging from congestive heart failure to hypothyroidism. There is no treatment for those disorders thought to be psychological in origin such as depression and related mood disorders. Likewise, no treatment for many disorders without a defined cause such as pre-senile dementia. But the real theater in modern medical practice today is mostly found in "preventive" medicine. As the author points out, much of this is justified by finding a couple of percentage point differences in real risk reduction over a few years in studies with variable exclusion criteria and composite end points largely driven by relatively soft components within them. Yet these types of "data" are often quoted to individual patients when they are given a specific range of "risk" for any of the common cardiovascular disorders over periods as long as ten or more years.
Much thanks for a thoughtful post. I am unsure whether I understand the gist of the discussion. My thoughts center around whether it really matters if a treatment effect rests upon biased assumptions. When considering a diagnosis of MDD or Alzheimer’s dementia, where the vagaries of human behavior are embedded in the definition no matter how rigorously it may be defined, it is inherently difficult to isolate a true treatment effect. Is this delineation important as long as the patient feels better and no major harm is identified? I am not clear on the answer.
I am wondering… it seems as if your argument asserts that, more often than not, my treatment interventions will have little and mostly limited effects, and there will be no way for me or the patient to determine or detect these. So, does this not mean we are all of us are engaged in a useless delusion of care which would best be abandoned once realized. Perhaps I should better spend my time learning to be a religious faith healer…?
Excellent analysis and conclusions.
The title is a bit baffling. On first glance it looks like the article was going to be about the effect of a physician's bedside manner on outcomes. It never mentions this element of care, but perhaps it suggests this indirectly. Given the very limited benefit from most prescriptions, it appears that a good physician takes up an actor-like role: He or she trots out the prescription pad, and states with gravitas and calm reassurance that this medication is 'just right for your depression'. -even while not really believing this is the case, just like the actor knows he really isn't Macbeth.
It’s even worse than this. Antidepressants are tested over very short time frames but prescribed for years or even a lifetime. Negative side effects accumulate with no benefit. A significant percentage have great difficulty discontinuing. Withdrawal symptoms from the drug are often mistaken for a relapse of depression. It’s remarkable how an educated society can be so brainwashed.
Yesssssss. Thank you for this.
Right on! Only puzzled by why you introduce the clinically irrelevant construct of the 'minimally important difference'
I think “minimally important difference” is used to illustrate how a study will report a treatment effect even when the magnitude of that effect is not enough to be perceived by the patient.
Biggest logic flaw of this essay is assuming each patient will only experience average treatment effect as measured by the clinical trial.
More realistically, some patients will benefit more and some will not. Non-responders will stop treatment. So actual treatment benefit on an responder may be a lot better than the average effect.
Trreatment may also include patient provider relationship…if the ere is even any time for that!
When it comes to depression, it's a bit more complicated. Classic MDD has been around since the dawn of mankind and is always associated with loss of appetite and weight loss. It is also very rare. Most people today have "atypical depression," which is associated with increased appetite and weight gain. It has only been around for about 70 years, since ultra-processed food took over our diet. In my opinion, atypical depression is caused by our modern diet and has nothing to do with MDD. I changed the name to Carbohydrate Associated Reversible Brain syndrome or CARB syndrome: https://carbsyndrome.com/
SSRI medication makes CARB syndrome worse over time, which really screws up any studies of depression.
In addition to incorrect dosing and natural history of the disease: another reason for treatment failure could be wrong diagnosis.
If prescribers would consider NNT/ ARR: the argument for reducing prescribing becomes more salient.
Excellent. 5 star article.