There are several wise comments here, I think. As a parent/caregiver who participates in some private social media groups where other parent/caregivers gather, I can unequivocally say the experiences that parents report of their children's responses to the same medication varies considerably within diagnoses. For that reason, as already pointed out by others, the mean response is a poor indicator of any individual patient's response. For this reason, parent/caregivers in the mentioned social media groups tend to avoid recommending a particular medication that is working well for their child to other parents. I have also noticed clinicians more often using phrases like "bipolar spectrum disorders" and "schizophrenia spectrum disorders" in what appears to be a nod in the direction of recognizing what we lump under a particular diagnosis is probably an assortment of different illnesses with similar symptoms. Likewise, perhaps depression is a spectrum of disorders with similar symptoms with the variability in the effectiveness of a medication among patients being partly related to those patients actually having different illnesses. There are so many unanswered questions in the complicated field of psychiatry that the safest position may be we simply don't know.
1. I was very surprised that there was not an in-depth discussion of antidepressant-induced mania and/or psychosis. Essentially any antidepressant can induce mania (unless it’s also an anti-manic or antipsychotic).
2. The majority of antidepressant suicides are people in their late teens and early 20s with a personal and/or family history of bipolarity or psychotic disorders. The state where a person is at highest risk of suicide is by far the bipolar mixed state especially if it is accompanied by psychotic features.
3. Psychiatry has been very bad at admitting to patients that despite our best judgment we sometimes make treatment choices that leave them worse off. That’s a fact of medicine to some extent. But our response is not.
4. When antidepressants induce mania the patient rarely gets the immediate attention from a clinician who recognizes the signs and more importantly the severity of this complication and how fragile it is going to make the patient for weeks or months. Often it is written off as initiation jitters and the dose is increased or a benzo script is written for a week or two. We aren’t rigorously honest about the dependency and the misery of discontinuation from long term use. We don’t adequately value the cost of sexual dysfunction on human wellbeing and drive to live or of weight gain in a person whose worst fear is feeling like they are fat and unattractive.
5. As a clinician I do get a bit tired of the endless ‘do SSRIs work’ slugfest because to me it is a) delusional but more importantly b) misses the whole point. First, from working in psych, I don’t see how a person could honestly say they don’t think they work. They obviously work. I simply don’t see how a person working with actual patients could say this with a straight face.
I’m open to the argument that they don’t work amazingly well, response rates aren’t great, relief is very partial, their side effects can be pretty bad for quality of life, the initiation period is uncomfortable and sometimes volatile, use in children and teens is not well studied at all, they often induce mania in latent bipolar or bipolar 2 presenting as chronic depression, it’s unclear (though many studies do find a prophylactic effect against future episodes) whether it leads to less of the lifespan being spent in states of depression. They’re overprescribed and used for things that obviously either require therapy or are normal human grief and transition processes that would probably resolve on their own. In fact, I think all these things are true.
Maybe you don’t see patients do well in the long-term. You might feel like it is a temporary aid with a long tail of dependence and side effects. You might view it as a dangerously understudied use of drugs that work most of the time but make things *way* worse frequently enough that they’re simply not worth messing with. All of these are valid arguments and thoughts I’ve had myself.
6. But to deny that they work would be to deny that the sky appears blue on a sunny summer’s day. It is interesting in that he does have actual clinical experience - I have noted that those making this argument and publishing the big popular books about how antidepressants don’t do anything are almost as a rule not written by medical professionals.
They’re pretty much always people from the social sciences or economics or physics world trying to come in, generally with a pretty obvious pre-existing bias, who insist that scientific rigor requires the exclusion of all clinical knowledge and experience we train in for years. I suppose David Healy is an exception, but I don’t think he says antidepressants are so dangerous as to be worthless. Certainly he doesn’t have a high opinion of them and is appalled by how widely they’re used but he doesn’t try to argue that they don’t help individual patients feel less depressed.
This argument seems much subtler, but I wish he would come out and state it directly rather than go full Emperor’s New Drugs. Because he’s clearly brilliant, so he knows the data and knows the drugs do work. After all, if they were inactive brand name sugar pills, then it would be bizarre to blame them for something as horrible as a suicide attempt. It seems highly unlikely to me that drugs with the potential to induce manic psychosis just aren’t doing much in the brain. Clearly they’re doing something!
If he wants to argue that the harm they’re doing is so severe, random, and greater in magnitude compared to the good, that’s a genuinely worthwhile discussion to have.
His argument seems to be that they don’t work nearly as much as we think and that they aren’t the risk-free drugs they can be portrayed as - and that this volatility and unpredictability happens widely and unpredictably enough that we should be much more cautious in our use of these drugs and analyzing assumptions about the long-term and population effects much more than we currently do.
7. I guess my litmus test for critical/anti-psychiatric value is does the argument still follow logical principles of non self-contradiction. I don’t expect somebody to articulate a full theory or anything, and I don’t expect a level of biological science knowledge equal to that of a medical professional.
But for me if you’re going to criticize antidepressants either argue:
A) they don’t really work
OR
B) they have horrible side effects and cause people to kill themselves and be addicted forever
Like....it just can’t be both ways. It seems like this critique refuses to pick a side and whenever it gets solidly refuted it transmutes or waveform collapses into whichever argument is left standing.
I refuse to believe that they’re placebos that also happen to cause otherwise non-suicidal people to kill themselves. I don’t know the secrets of the brain, but I do know that they can’t be *both* of those things.
I would like to thank Dr. Plöderl and Dr. Aftab for an enlightening discussion of this complex and controversial topic. As a (now retired) specialist in adult mood disorders, I acknowledge the uncertainties inherent in studies of SSRIs/SNRIs and suicidality; however, I believe the preponderance of the evidence does not support the claim that these agents increase suicidality (a vague term, to be sure) or completed suicide in adult patients 25 years and older. And, there are at least some data pointing to a reduction of suicidality (suicide attempts) in antidepressant-treated patients age 65 and older, as the discussion with Dr. Plöderl notes (Stone et al, 2009)
A recent, carefully-done, observational study by Lagerberg et al generally supports the above conclusions. The authors write:
"We found an increased risk of suicidal behaviour among individuals aged below 25 years who were treated with an SSRI after a depression diagnosis as compared to those who were not. We found no evidence of an effect among older age categories. The results are similar to those from RCTs, lending validity to this observational study. However, the issue of unmeasured confounding remains, and studies from data sources with more detailed information on confounders—notably depression severity—are called for. Our results confirm that individuals with a history of suicidal behaviour are a high-risk group, but we found no evidence that SSRI initiation conferred elevated risks of suicidal behaviour in this subgroup." [1]
Like all observational studies, this one has both strengths and limitations, as the authors acknowledge.
Finally, I would like to comment on the statement that,
"Put differently, the claim that “antidepressants are live-saving” is not supported by the evidence, at least not for the average patient."
Clinicians, of course, do not treat "the average" patient or an aggregate of patients. Each patient we treat is unique. Having treated many hundreds of severely depressed patients over the course of more than 25 years--many of whom I followed closely for 2, 3 or more years--I have certainly seen many whose suicidal ideation or impulses diminished greatly in the course of antidepressant treatment.
I am well aware that such observations are often dismissed as "anecdotal" or the result of an unacknowledged "placebo effect." Yet when this observation is made dozens and dozens of times, in patients whose depression did not respond to two or three adequate antidepressant trials, but did respond to the fourth agent, the clinician is naturally reluctant to accept the, "it was just a placebo effect" explanation. In such cases, I believe it is entirely appropriate to say that the totality of treatment--antidepressant plus the therapeutic alliance, probably acting synergistically--was indeed "life-saving."
Thanks again to you both for this useful discussion!
Respectfully,
Ronald W. Pies, MD
Professor Emeritus of Psychiatry
1. Lagerberg, T., Matthews, A.A., Zhu, N. et al. Effect of selective serotonin reuptake inhibitor treatment following diagnosis of depression on suicidal behaviour risk: a target trial emulation. Neuropsychopharmacol. 48, 1760–1768 (2023). https://doi.org/10.1038/s41386-023-01676-3
Something that I really would love to see an article or interview with you about Dr. Aftab: the scientific validity (or rather invalidity) of psychiatric nosology.
As others touched on - MDD is heterogenous, and as others have argued elsewhere - we have subsumed many bipolar spectra and cyclothymic temperaments under MDD.
It certainly dovetails with the observation of antidepressant induced suicidality, specifically that many individuals who are becoming activated, anxious, suicidal with antidepressants. As many will argue, the index episode of bipolar is depression, and the onset of illness is a median of 19, a full decade before MDD typically. It would be no wonder then that the signal for suicidality would strengthen with younger age.
Our ability to see not only adverse effects, but to understand genuine efficacy (antidepressants, as you have touched on, significantly help a certain proportion of patients, and it is often obscured by the “average” effect sizes we see) has been hampered by the rigidity of the DSM in many ways, and specifically the FDA’s reliance on broad, often invalid DSM diagnoses in order to seek approval.
There are several wise comments here, I think. As a parent/caregiver who participates in some private social media groups where other parent/caregivers gather, I can unequivocally say the experiences that parents report of their children's responses to the same medication varies considerably within diagnoses. For that reason, as already pointed out by others, the mean response is a poor indicator of any individual patient's response. For this reason, parent/caregivers in the mentioned social media groups tend to avoid recommending a particular medication that is working well for their child to other parents. I have also noticed clinicians more often using phrases like "bipolar spectrum disorders" and "schizophrenia spectrum disorders" in what appears to be a nod in the direction of recognizing what we lump under a particular diagnosis is probably an assortment of different illnesses with similar symptoms. Likewise, perhaps depression is a spectrum of disorders with similar symptoms with the variability in the effectiveness of a medication among patients being partly related to those patients actually having different illnesses. There are so many unanswered questions in the complicated field of psychiatry that the safest position may be we simply don't know.
1. I was very surprised that there was not an in-depth discussion of antidepressant-induced mania and/or psychosis. Essentially any antidepressant can induce mania (unless it’s also an anti-manic or antipsychotic).
2. The majority of antidepressant suicides are people in their late teens and early 20s with a personal and/or family history of bipolarity or psychotic disorders. The state where a person is at highest risk of suicide is by far the bipolar mixed state especially if it is accompanied by psychotic features.
3. Psychiatry has been very bad at admitting to patients that despite our best judgment we sometimes make treatment choices that leave them worse off. That’s a fact of medicine to some extent. But our response is not.
4. When antidepressants induce mania the patient rarely gets the immediate attention from a clinician who recognizes the signs and more importantly the severity of this complication and how fragile it is going to make the patient for weeks or months. Often it is written off as initiation jitters and the dose is increased or a benzo script is written for a week or two. We aren’t rigorously honest about the dependency and the misery of discontinuation from long term use. We don’t adequately value the cost of sexual dysfunction on human wellbeing and drive to live or of weight gain in a person whose worst fear is feeling like they are fat and unattractive.
5. As a clinician I do get a bit tired of the endless ‘do SSRIs work’ slugfest because to me it is a) delusional but more importantly b) misses the whole point. First, from working in psych, I don’t see how a person could honestly say they don’t think they work. They obviously work. I simply don’t see how a person working with actual patients could say this with a straight face.
I’m open to the argument that they don’t work amazingly well, response rates aren’t great, relief is very partial, their side effects can be pretty bad for quality of life, the initiation period is uncomfortable and sometimes volatile, use in children and teens is not well studied at all, they often induce mania in latent bipolar or bipolar 2 presenting as chronic depression, it’s unclear (though many studies do find a prophylactic effect against future episodes) whether it leads to less of the lifespan being spent in states of depression. They’re overprescribed and used for things that obviously either require therapy or are normal human grief and transition processes that would probably resolve on their own. In fact, I think all these things are true.
Maybe you don’t see patients do well in the long-term. You might feel like it is a temporary aid with a long tail of dependence and side effects. You might view it as a dangerously understudied use of drugs that work most of the time but make things *way* worse frequently enough that they’re simply not worth messing with. All of these are valid arguments and thoughts I’ve had myself.
6. But to deny that they work would be to deny that the sky appears blue on a sunny summer’s day. It is interesting in that he does have actual clinical experience - I have noted that those making this argument and publishing the big popular books about how antidepressants don’t do anything are almost as a rule not written by medical professionals.
They’re pretty much always people from the social sciences or economics or physics world trying to come in, generally with a pretty obvious pre-existing bias, who insist that scientific rigor requires the exclusion of all clinical knowledge and experience we train in for years. I suppose David Healy is an exception, but I don’t think he says antidepressants are so dangerous as to be worthless. Certainly he doesn’t have a high opinion of them and is appalled by how widely they’re used but he doesn’t try to argue that they don’t help individual patients feel less depressed.
This argument seems much subtler, but I wish he would come out and state it directly rather than go full Emperor’s New Drugs. Because he’s clearly brilliant, so he knows the data and knows the drugs do work. After all, if they were inactive brand name sugar pills, then it would be bizarre to blame them for something as horrible as a suicide attempt. It seems highly unlikely to me that drugs with the potential to induce manic psychosis just aren’t doing much in the brain. Clearly they’re doing something!
If he wants to argue that the harm they’re doing is so severe, random, and greater in magnitude compared to the good, that’s a genuinely worthwhile discussion to have.
His argument seems to be that they don’t work nearly as much as we think and that they aren’t the risk-free drugs they can be portrayed as - and that this volatility and unpredictability happens widely and unpredictably enough that we should be much more cautious in our use of these drugs and analyzing assumptions about the long-term and population effects much more than we currently do.
7. I guess my litmus test for critical/anti-psychiatric value is does the argument still follow logical principles of non self-contradiction. I don’t expect somebody to articulate a full theory or anything, and I don’t expect a level of biological science knowledge equal to that of a medical professional.
But for me if you’re going to criticize antidepressants either argue:
A) they don’t really work
OR
B) they have horrible side effects and cause people to kill themselves and be addicted forever
Like....it just can’t be both ways. It seems like this critique refuses to pick a side and whenever it gets solidly refuted it transmutes or waveform collapses into whichever argument is left standing.
I refuse to believe that they’re placebos that also happen to cause otherwise non-suicidal people to kill themselves. I don’t know the secrets of the brain, but I do know that they can’t be *both* of those things.
I would like to thank Dr. Plöderl and Dr. Aftab for an enlightening discussion of this complex and controversial topic. As a (now retired) specialist in adult mood disorders, I acknowledge the uncertainties inherent in studies of SSRIs/SNRIs and suicidality; however, I believe the preponderance of the evidence does not support the claim that these agents increase suicidality (a vague term, to be sure) or completed suicide in adult patients 25 years and older. And, there are at least some data pointing to a reduction of suicidality (suicide attempts) in antidepressant-treated patients age 65 and older, as the discussion with Dr. Plöderl notes (Stone et al, 2009)
A recent, carefully-done, observational study by Lagerberg et al generally supports the above conclusions. The authors write:
"We found an increased risk of suicidal behaviour among individuals aged below 25 years who were treated with an SSRI after a depression diagnosis as compared to those who were not. We found no evidence of an effect among older age categories. The results are similar to those from RCTs, lending validity to this observational study. However, the issue of unmeasured confounding remains, and studies from data sources with more detailed information on confounders—notably depression severity—are called for. Our results confirm that individuals with a history of suicidal behaviour are a high-risk group, but we found no evidence that SSRI initiation conferred elevated risks of suicidal behaviour in this subgroup." [1]
Like all observational studies, this one has both strengths and limitations, as the authors acknowledge.
Finally, I would like to comment on the statement that,
"Put differently, the claim that “antidepressants are live-saving” is not supported by the evidence, at least not for the average patient."
Clinicians, of course, do not treat "the average" patient or an aggregate of patients. Each patient we treat is unique. Having treated many hundreds of severely depressed patients over the course of more than 25 years--many of whom I followed closely for 2, 3 or more years--I have certainly seen many whose suicidal ideation or impulses diminished greatly in the course of antidepressant treatment.
I am well aware that such observations are often dismissed as "anecdotal" or the result of an unacknowledged "placebo effect." Yet when this observation is made dozens and dozens of times, in patients whose depression did not respond to two or three adequate antidepressant trials, but did respond to the fourth agent, the clinician is naturally reluctant to accept the, "it was just a placebo effect" explanation. In such cases, I believe it is entirely appropriate to say that the totality of treatment--antidepressant plus the therapeutic alliance, probably acting synergistically--was indeed "life-saving."
Thanks again to you both for this useful discussion!
Respectfully,
Ronald W. Pies, MD
Professor Emeritus of Psychiatry
1. Lagerberg, T., Matthews, A.A., Zhu, N. et al. Effect of selective serotonin reuptake inhibitor treatment following diagnosis of depression on suicidal behaviour risk: a target trial emulation. Neuropsychopharmacol. 48, 1760–1768 (2023). https://doi.org/10.1038/s41386-023-01676-3
Something that I really would love to see an article or interview with you about Dr. Aftab: the scientific validity (or rather invalidity) of psychiatric nosology.
As others touched on - MDD is heterogenous, and as others have argued elsewhere - we have subsumed many bipolar spectra and cyclothymic temperaments under MDD.
It certainly dovetails with the observation of antidepressant induced suicidality, specifically that many individuals who are becoming activated, anxious, suicidal with antidepressants. As many will argue, the index episode of bipolar is depression, and the onset of illness is a median of 19, a full decade before MDD typically. It would be no wonder then that the signal for suicidality would strengthen with younger age.
Our ability to see not only adverse effects, but to understand genuine efficacy (antidepressants, as you have touched on, significantly help a certain proportion of patients, and it is often obscured by the “average” effect sizes we see) has been hampered by the rigidity of the DSM in many ways, and specifically the FDA’s reliance on broad, often invalid DSM diagnoses in order to seek approval.
Excellent discussion. Thank you.