December 22, 2008

Major Depression is Major Depression, Until Proven Otherwise


In which Marco Polo is forced to agree that a unicorn is a unicorn, until proven otherwise.

Ronald Pies gives a critique of the Horowitz and Wakefield book, "The Loss of Sadness."  (This is the same book Dr. Nasrallah dismissed in an another editorial.)

His article is very good, and aptly represents the "con" position to Horowitz-Wakefield's thesis that that normal sadness has been pathologized into MDD.

Pies summarizes his position in bullet points at the beginning:

  • does  bereavement predict a benign, self-limited course even when the person meets all the criteria for MDD?
  • does MDD in the context of bereavement differ, and respond to treatment differently, than typical MDD?
  • do psychiatrists have any way to fairly judge what is proportionate and disproportionate grief?  Are there clinically validated instruments to do this?
And since the anwer to these is no-- there is very little evidence for such distinction between bereavement-associated depression (BRD) and typical MDD, one should not attempt to make such a distinction: MDD, when it fits the criteria, is MDD.  Go.


Putting aside any debate as to whether or not Pies is right, a more important question is this: do we want him to be right?

We should not be too quick to pathologize, even when there is pathology, because  pathologization reflexively diminishes the individual's ownership.  Not just their "responsibility"-- that they had a hand in the pathology, and have a hand in the treatment (not as blame but merely as description of events) but also their identity.  The moment sadness becomes MDD, even legitimately, it becomes less something that is them and more something that occurred to them.  Grief is my response to loss; MDD is my body's response to loss.  That's a big difference. The quick retort is that MDD does not seek to reduce identity ownership of "symptoms."  Maybe-- but it does anyway.  A second retort is that this reduction is a good thing.  Again, maybe, on a case by case basis, but as a general axiom for humanity, it can't be.


But aside from abstract ideas about identity, the main thrust of Pies's argument is the lack of evidence for a distinction between BRD and MDD.

...common sense might tell us that bereavement related depression is a normal, "adaptive" response to loss, whose "biology" and response to antidepressants would differ considerably from that of standard major depression.  This is all quite common sensical-- and all quite qwithout convincing evidence.
Does common sense say that? I assume he means "common sense would say bereavement wouldn't respond to antidepressants," but response to "antidepressants" is certainly no criterion for making a diagnosis.   We're not even sure that SSRIs work for typical MDD, let alone bereavement-- consider the hardly impressive 10% improvement over placebo-- even as 50% of studies in which SSRIs don't beat placebos lay unexposed on the laptops of a hundred tenure track academics like so many unerased browser caches: a little guilt, a little embarrassment, a lot of denial.  "That didn't really count."  Honi soit qui mal y pense. 

And response to which antidepressant?  MAOIs?  SSRIs?  Seroquel?  All of these FDA approved antidepressants tell us nothing about the underlying pathology, if it even is the same pathology.  It doesn't even tell us anything about antidepressants themsleves.  The fact that only Wellbutrin worked in one guy and Zoloft in the other doesn't suggest that MDD can have multiple treatments, but that those two guys have different problems.  Consider, in 2001, a patient with pure MDD is treated with Seroquel monotherapy.  Do you say Seroquel is an antidepressant, or do you say the guy's "real" diagnosis was bipolar? It is only an accident of history that Seroquel is an anipsychotic now indicated for MDD, and not an antidepressant we later find out is an antipsychotic. 

If otitis media resolves because of antibiotic treatment, does that mean that it was bacterial?  And if we later discover that it was indeed viral, does that mean that the antibiotic actually did nothing?  Are you sure?  Sometimes we discover medicines do things we didn't know about; sometimes there is placebo effect, which still counts as the medicine doing something; sometimes what you think is the actual medicine is decoy: valproic acid was originally simply an organic solvent, once used as a vehicle to test novel antiepileptics.

The fact that I can knock 12 points off a Hamilton Depression scale with an Ambien and BID  Krispy Kream should serve as a warning about the validity and generalizability of the term "antidepressant." 

Psychiatry can live with unknowns as long as it doesn't try to assume pathology by the presence or absence of efficacy.  So I agree with Pies-- you can't assume SSRIs won't work in BRD.  But I also disagree: so what?


Pies makes a mistake many doctors make: choosing science that suits a social agenda.  This isn't malicious, he is doing it as a healer, in the service of humanity.  But it is an agenda nonetheless.  The entire article's logic and evidence is solely to promote a single idea that finally appears in the last sentence:

It would be tragic if we inadvertently discouraged recently bereaved persons from seeking professional help, on the dubious presumption that  that their depressive symptoms are merely "normal adaptations" to loss.
That's the main concern: that we don't discourage people from seeking help, that we don't turn people away because we think they don't have MDD.

It's possible that he wrote this in 1955, but a cursory examination of the state of affairs in 2008 fairly quickly makes evident that quite the opposite is the current state of affairs.

Are we in any danger of not treating people who want it?  If Pies accepts a broad definition of treatment to include non-antidepressant treatments, e.g.  therapy, sleeping medications, etc-- does it happen ever that psychiatrists turn patients away at the door?  "Wait, wait-- all this is because your husband died?  Get the hell out of here, you abuser of the system."

Certainly I can agree with him that more rigorous application of the criteria would help formalize who gets and does not get treatment; but simply to the question of whether we face a dire emergency of undertreating sadness-- whatever we later decide to call it-- seems to contradict reality.

Even if we grant his worries that it could happen that we turn people away, it isn't at all evident that doing this harms humanity.  On the one hand is the not well founded belief that our treatments actually do anyone any good-- see above.  "Depression is a lethal condition."  Ok-- what reduces that lethality?  Not antidepressants, as far as I can tell.   Etc.  And depression isn't always a lethal condition, indeed, it is rarely a lethal condition.  Lung cancer is a very lethal condition, but there is no rush to assume that chronic cough is cancer,  even if they smoke 3 packs a day.  There is nothing, beyond an odd claim to individual rights, to gain from allowing coughing smokers to buy more cigarettes, but there may be quite a bit to gain from not pathologizing bereavement even when it is MDD.  It doesn't mean we can't help them-- and this is indeed Pies's point-- and we should help them, maybe even give them an SSRI-- but that act must be done in the context of bereavement, not in the context of depression.

As if to reinforce my point, Pies writes:

...on the dubious assumption that their depressive symptoms are merely "normal adaptations [sic]" to loss.

It's hard to tell if he meant to do this, or it was a slip, but note his word choice.  The correct word should be "adaption," not adaptation.  An "adaption" is a change in response to surroundings, events.  An "adaptation" is the process of adapting, it is what increases evolutionary fitness in a species. It doesn't help that single organism, it helps the species.   In that context, how society grieves could be an adaptation; but making it MDD precludes that possibility because we define it as not beneficial to the species.


If the purpose of the criteria is to make the diagnosis, then we might want to ask what is the purpose of treatment.  Assume someone with BRD was treated such that within, say, a month, all of their symptoms resolved.  Completely.  Would you call that a treatment success, or a treatment failure?  Only one of those is defined by the current system of psychiatry.


Pies attacks the concept of a "trigger" for depression.  It looks like the depression came as the result of the recent death, but who knows?  We often assign a trigger in retrospect, but that may simply be the mind retrofitting a cause, and not actually observing observing a necessary connection.  Well played, Dr. Hume. 

I agree: ignoring issues of causality and focusing only on the criteria would be both fair and awesome except that the criteria lead to a diagnosis about which causality is implied: amines, genetics, and the like.   It's one thing to debate whether BRD and MDD share similar biology, or not; but it isn't at all evident that cases of typical MDD share common biology, or biology at all, yet that is precisely what is assumed.  Does every person with MDD have a genetic basis for it?   Yet no psychiatrist ever says, "this is MDD, but I doubt you have a genetic predisposition."  

The problem is that such assumptions of biology-- even if they have basis-- create social and legal obligations. Example: until you have hard evidence to the contrary, you want it to be bereavement, not MDD, so that you can't be involuntarily committed for it.  You want the commitment to be about the possible dangerous behavior (e.g. evidence of suicide) and not at all the about the diagnosis.  You say: but we don't commit people for being depressed.  You don't.  Today you don't.  But tomorrow?  Don't make the Fundamental Error Of The Dumbest Generation of Narcissists In The History Of The World: today is the end of history.  We once thought homosexuality was a disease; today we don't; and one day we will think so again.  It is inevitable.  Science is almost never fast enough to prevent the mission creep of our own prejudices.


I would like to request tha... (Below threshold)

December 22, 2008 7:26 PM | Posted by jessa: | Reply

I would like to request that you write more about something you only mentioned here in a cursory way; you say, "The fact that only Wellbutrin worked in one guy and Zoloft in the other doesn't suggest that MDD can have multiple treatments, but that those two guys have different problems." I'm not certain I agree with you 100% on that, as I would be more inclined to say that this suggests that those two guys MAY have different problems.

Qualifiers aside, this is something I have thought about a lot but not really heard anywhere else. In all of those studies they treat depression as a constant because all the patients fit the diagnostic criteria for depression, but I don't think that is a defensible position to take. Diagnostic criteria are put together, as best as I understand, by looking at lots of patients and noticing that certain symptoms seem to occur in tandem. For my purposes here, I don't find that objectionable, but I do think it is erroneous to subsequently take those vaguely defined diagnoses and use them as constants in scientific experiments.

I'm disappointed that I haven't seen this mentioned more because I think that its recognition could be valuable in the study of depression and other kinds of mental illness. Recognizing this might make studying the treatment of mental illness much more complicated, but researchers could get on with the work of that difficult untangling of factors instead of spending time and money on studies that have no useful applications since we don't know what depression is. Perhaps this is something that I just don't realize has already been considered and thrown by the wayside as a useless consideration? (I'm young, I've only just completed a bachelor's degree, so while I know I'm no dummy, I also tend to doubt that I am seeing something that no one else notices.)

Vote up Vote down Report this comment Score: 4 (4 votes cast)
Multiple prevalent trends--... (Below threshold)

December 22, 2008 8:40 PM | Posted by Novalis: | Reply

Multiple prevalent trends--cognitive inertia, the need to feel useful, and financial interest, to name just three--bias psychiatrists toward interpreting the range of psychopathology generously. Only a few, rather less common influences--philosophical scruple and sheer contrarianism--act as mitigating factors.

Vote up Vote down Report this comment Score: 1 (1 votes cast)
Your point isn't inciden... (Below threshold)

December 22, 2008 9:32 PM | Posted, in reply to jessa's comment, by Alone: | Reply

Your point isn't incidental to the overall dialogue, it is the ONLY point that is relevant.

When criteria for MDD are met, be it in clinical practice, in a epidemiological study, or in a clinical trial, that entity is assumed to carry a lot of baggage, in the same way he diagnosis of, say, diabetes carries a lot of baggage. But all of these may use entirely different criteria for "MDD." e.g. retrospective reviews rely on the psychiatrist; clinical trials rely on the Hamilton, etc.

My point about Wellbutrin and Zoloft was that differential treatment responses tell us absolutely nothing about the underlying pathology. Maybe they're the same; maybe they're entirely different. We rely on the nomenclature of "antidepressant" to tie them together, but who knows? Hence my Seroquel point-- five years ago we would have suspected it was bipolar. OR, we rely on the Hamilton to tease out antidepressant efficacy (still not a reason to think all MDDs are the same): but my point about donuts and Ambien is that I can achieve better response on a Hamilton with that then with Zoloft. So now what?

The best analogy for MDD isn't cancer or diabetes, but hypercholesterolemia. Hypercholesterolemia isn't a disease, it's a symptom of another disease, for example CAD or Familial Hypercholesterolemia. It sounds plausible to pathologize hypercholesterolemia, but it ignores reality: is high cholesterol always pathological? Indeed, there may come a time where we discover that high cholesterol is protective in some other disease-- suicide?-- such that a doctor has to decide which is preferable for the patient in front of him-- no longer can we make the blanket statement that cholesterol over 250 requires treatment.

It's ok to generalize, or lump together, all the different kinds of MDD as a first step, e.g., "we don't know if these are biologically the same, but they appear similar, so we're going to recommend these treatments." That would be ok. The problem is that once we lump them all together, we then make the assumption that they all have something in else common other than their appearance. To show you how preposterous this is, I'll give you a pharmacology example: oh, we just discovered that lithium is effective in MDD. Despite the evidence that lithium is protective in suicide, we must put a black box warning about it doubling the suicide risk, since it is now an "antidepressant."

That kind of classism would get you killed 91 years ago. But since we're at the end of history, no worries.

But diabetes has logical, necessary baggage, and

Vote up Vote down Report this comment Score: 3 (3 votes cast)
I can't help but think many... (Below threshold)

December 22, 2008 11:12 PM | Posted by David : | Reply

I can't help but think many of the issues brought up in this posting have more to do with the dominance of the pharmacological model than anything else. If I was, for example, looking at the functional aspects of what is being referred to as MDD from a clinical perspective, based on the presenting symptoms of an individual, I would be looking at what treatment modality might be most efficacious, with the least serious side-effects (including patholgizing/institutionalizing said state of being).

Am I treating a patient or a disease? Is there a continuum of therapeutic intervention, beginning with the least intrusive procedures and then escalating, based on response? Or is it SOP to throw a "broad-spectrum" response, period?

If it's a pharmacological paradigm, these questions have some really cut and dried answers, especially given the current pathways to funding ... without a doubt insurance and the industry favors medication over alternative, individualized, and adaptive approaches.

Vote up Vote down Report this comment Score: 0 (0 votes cast)
I'm so very very with you o... (Below threshold)

December 22, 2008 11:34 PM | Posted by jessa: | Reply

I'm so very very with you on this, that just because we have one name for something doesn't mean that it is only one thing, re: depression, and that just because something can be a negative doesn't mean it always it, re: high cholesterol.

But to take it out of the purely theoretical, is anyone doing anything about this? (Beyond this issue, I could ask similar questions about so many of the topics you post about here.) Is it that not everyone sees these flaws in their methodology and we need to do a better job of exposing them? Is it that everyone notices these and we need to do a better job of making people care? Am I right in thinking that it could do a lot of good if these ideas were taken into account in experimental studies? Where are the people who do these things? How do they do them?

Vote up Vote down Report this comment Score: 1 (1 votes cast)
jessa: Speaking as a Britis... (Below threshold)

December 23, 2008 5:17 AM | Posted by Neuroskeptic: | Reply

jessa: Speaking as a British researcher, almost everyone I've met would agree with the thrust of what you're saying. Everyone agrees that MDD is not a single entity. The clinicians know this from experience, researchers know this from reading the literature. Even my undergrad students very quickly come to accept it. I've never met a single person who's defended the idea that MDD is a single disease.

So the problem is not that people like the current state of affairs, the problem is that they (we) see it as the best possible. Depression, as a state of mind, obviously exists. In order to work with it (clinically or scientifically) you have to have criteria for diagnosing it. DSM-IV criteria are as good as any other.

We would be overjoyed if someone were to discover a sub-type of depression which was different to all other kinds of depression - say, a subtype of depression with a characteristic pattern of symptoms, a clear pathology and associated with a single genetic marker. If that happened it would be the discovery of the year and everyone would quickly put it into practice. The problem is that no such subtype has yet emerged. And people are sufficiently skeptical that it ever will, that no-one is spending time looking.

Subtyping depression has been the dream for 60 years, not much has come of it. Although people say that "atypical" depression (eat more, sleep more, tired) seems to respond better to MAOis than tricyclics, and "melancholia" (eat less, sleep less, wake up at 4am, rumination) seems to respond well to ECT and drugs and poorly to placebo & psychotherapy. There are also some interesting biological aspects to melancholia (endocrine abnormalities, sleep cycle abnormalities) but few people are researching them any more because they're nothing to do with monoamines. Although given that the next generation of antidepressants include drugs targeting the neuroendocrine systems and melatonin receptors (=sleep) maybe this will change...

Vote up Vote down Report this comment Score: 1 (1 votes cast)
I think that the trick here... (Below threshold)

December 23, 2008 5:29 AM | Posted by Trei: | Reply

I think that the trick here is - do we want it to?

The one thing we can count on is that tommorow we'll know more. I can't imagine anyone with more than 2 neurons debating this.

So while looking for answers is nice, thinking that we already have them is dangerous; it's more pride than smarts. It's foolishness.

Sure, most scientists are actually short, bald guys, with glasses, and their knowledge of today is their only chance to over-compensate that nasty feeling of 'you'll never get The Girl, you nerd!'

wouldn't it be wiser for all of us to stop serving their egos and look after our own interests first?
this is the kind of problem that can never be solved completely. we never know for sure. we may think we need to choose between a) and b), but that's just today. There may be a c) or d) or even a z) that we're not even aware of - and those will become known to our grand-grand...children.

for now, I think it's wiser to ask ourselves what's to gain and what's to loose in any of these choices? What's the path before any decission? Words are just words. We can call is 'depression', or 'sadness', or 'bjvhjC'. Is it in our best interest to call it that?

after the 'naming', come certain actions connected to that specific 'name'. Are those the consequences we want? Will they make us into 'who' or 'what' we want to be tomorrow?

Vote up Vote down Report this comment Score: 0 (2 votes cast)
neuroskeptic: I fe... (Below threshold)

December 23, 2008 10:14 AM | Posted by jessa: | Reply


I feel much better now knowing that I am not alone in recognizing that there may be many types of depression. But it is also disappointing that this hasn't been terribly helpful anyhow.

Even if we aren't currently able to tease out subtypes of depression, though, is there no way for this recognition to add insight into the research that is currently being done? It seems that there have been several news stories of studies recently that say things like, "exercise is every bit as effective as anti-depressants," or "anti-depressants are no more effective than placebos." Perhaps this is just that mass media is perpetuating their misunderstanding of these studies. Just because exercise and anti-depressants produce improvement in the same percentage of patients doesn't mean that they are equal, because there may be no single patient for whom exercise and anti-depressants both work. If it is just the popular media with this misconception, I still think it would be worth fixing those misconceptions. But in the few studies I have read directly, I haven't seen this consideration come into the conclusion-drawing process of the researchers either. This is maybe on account of my limited experience, but maybe not.

In terms of using this information in practice, in actual mental health CARE, I'm not seeing it. If we recognize that there are many different sorts of depression for which different treatments are effective, on account of both depression subtype and non-pathological personality sorts of differences, why is there such a one-size-fits-all approach to treatment? I'm all for trying lots of different things, but medications and psychotherapies tend to be the only varieties (in my experience), even though there are many other treatments that have been effective, so why not try those? (Perhaps this is about what treatments insurance companies trust?) And if we know that there are different sorts of depression that respond to different sorts of treatment, why are some treatments tried over and over even when they have never worked? I understand that there needs to be adequate trials of different treatments in order to demonstrate their effectiveness or lack thereof, but when that lack has been demonstrated, why continue? (Again, this has been my experience and perhaps is not the norm.)

Vote up Vote down Report this comment Score: 1 (1 votes cast)
I'm not a professional, so ... (Below threshold)

December 23, 2008 12:50 PM | Posted by La BellaDonna: | Reply

I'm not a professional, so I hope folks will allow me some leeway, and offer additional clarification, as necessary.

Is it possible - am I correct in interpreting Pies's writing correctly? Does he actually think that there is something abnormal and unhealthy at work when an individual grieves at the death of someone dear to that individual?

Alone's response: no, he doesn't say bereavement is abnormal. He means that when bereavement is so severe that the person meets criteria for MDD, then it should be considered MDD, not bereavement-- so you would treat it the same, etc. In other words, bereavement may take different forms, but when it passes the threshold for MDD, that changes its character.

Vote up Vote down Report this comment Score: 1 (1 votes cast)
If you view "depression" as... (Below threshold)

December 23, 2008 1:34 PM | Posted, in reply to jessa's comment, by Anonymous: | Reply

If you view "depression" as a general response to some type of un-met need, then, of course, there are many types of general responses to un-met needs. The person is not getting something it needs--if that something is a feeling of security that results in unrestful sleep, then the "depression" scores will improve with Ambien.

Interestingly, if the sole effect of SSRIs was the inducement of an attitude known as "not giving a shit", this would still explain how it "treats" its broad range of "disorders."

Vote up Vote down Report this comment Score: 1 (1 votes cast)
>Grief is my response to lo... (Below threshold)

December 23, 2008 3:08 PM | Posted by spriteless: | Reply

>Grief is my response to loss; MDD is my body's response to loss. That's a big difference.

No it's not. Not to everyone. Appreciation is my body's response to good poetry, hyper is my body's response to caffeine, it's not as if my brain isn't me, isn't a part of my body.

Vote up Vote down Report this comment Score: 1 (1 votes cast)
Maybe I'm very old-fashione... (Below threshold)

December 25, 2008 5:50 AM | Posted by Nobody: | Reply

Maybe I'm very old-fashioned. But the only thing that worries me is what effect these meds will have on the genetic material of humanity. Since everyone appears to be taking them these days, especially young women...

Vote up Vote down Report this comment Score: 1 (1 votes cast)
I agree to an extent about ... (Below threshold)

March 1, 2012 7:19 PM | Posted by Anonymous: | Reply

I agree to an extent about not "pathologizing" a person when they could be experiencing something like bereavement. That could be bad for some people, to have it labeled depression. On the other hand though, some people (myself, on occasion) need to see it as a serious mental illness in order to take the meds and the therapy seriously. Also, sometimes (actually often) people need a break from struggling with an illness that rests, in their mind, on their own shoulders; labeling it depression could actually make a person relax for a bit, which could be healthy. Blah, blah, blah. So many possible ways to look at things. It leads me to one thing I suspect is true: all of this makes me think psychiatry, although considered a science, has to be equally an art.

Vote up Vote down Report this comment Score: 0 (2 votes cast)
That's what he said. Note t... (Below threshold)

March 20, 2013 1:04 AM | Posted, in reply to jessa's comment, by Atarii: | Reply

That's what he said. Note the word "suggests," rather than "proves."

Vote up Vote down Report this comment Score: 0 (0 votes cast)