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.