April 4, 2007

Farewell, Depression



Write this day down: 4/4/07, it is the first day of the new psychiatry.  Everything changes, starting today.

Today, in the New England Journal Of Medicine, is an article ostensibly about the lack of additional benefit from adding an antidepressant to a mood stabilizer.  This is both surprising and not surprising: surprising, because, well, you'd think two drugs would be better than one.  Not surprising because, well, if the first drug worked, why would a second even be necessary?  (See #8). And if the first didn't work, how do you know the improvement didn't come entirely from the second drug

If this is all the article said, it would not be worthy of mention, let alone the herald of a new dynasty.

The study also found that the studied antidepressants did not induce mania.  That this should have been prima facie obvious even to a 9 year old without the benefit of eyes (what's an antidepressant?  They're not all chemically similar, so why should they all be blamed for the same side effects?) isn't the point here. 

The true importance of the study is contained in three statements.  If you blinked, you would have missed them.

The first is this:

Mood stabilizers were initially limited to lithium, valproate, the combination of lithium and valproate, or carbamazepine. In 2004, the protocol was amended to define mood stabilizers operationally as any FDA-approved antimanic agent.


The second is this, from the abstract:

Our study was designed to determine whether adjunctive antidepressant therapy reduces symptoms of bipolar depression...


And the third is this:

In summary, for the treatment of bipolar depression, we found that mood-stabilizing monotherapy provides as much benefit as treatment with mood stabilizers combined with a standard antidepressant.


Psychiatry is not about science, it is about language, politics.  What's happened here is that "mood stabilizer" now includes atypical antipsychotics; and-- compare what the study was designed to show and what they spun it to show-- we've gone from "polypharmacy is not better" to "monotherapy with mood stabilizers [read: antipsychotics] is just as good as two drugs at once." 

There's a subtlety there, and that subtlety is magnificent.

Note the authors: Sachs, Bowden, Calabrese, Thase, etc-- the same people who pushed psychiatry into flowchart polypharmacy; where Depakote was always first line for all phases of bipolar disorder, and any exacerbations that developed were treated with the addition of a second medication.

What the article is saying is that academic psychiatrists are no longer behind antidepressants and antiepileptics.  SSRI and SNRI use will decline from here, as will Depakote.  They're behind antispychotics.  And antipsychotic use is positioned to explode. 

It goes without saying: only the antipsychotics are still branded.

But without academics pushing SSRIs, their use will wane--and, importantly, so will their support of the diagnosis "Major Depression."  This is going to sound controversial, inane, but it will happen.

Look for upcoming articles finding that "Depression" is overdiagnosed, that it is really just-- life.  Look for articles that now find SSRIs aren't that effective after all, that the old "10% better than placebo" is a statistical trick with little clinical utility.  That they are way overused in kids.

You might say, wait, isn't the decline of polypharmacy  a good thing; that SSRIs are overused in kids; that they aren't that great; and that depression is overdiagnosed?  All of this is true, but this isn't psychiatry finally coming to its senses; this is psychiatry entering the manic phase.  Sure, it's less SSRIs for kids; but it's more antipsychotics.

Because simultaneously there will be articles pushing the idea that recurrent unipolar depression is really bipolar depression; that there are common genetic or heritability patterns; that the epidemiology and course is similar, etc. The move will be to squeeze out MDD into "life" and bipolar.  This done, antipsychotics become first line agents.  Oh, and look for antipsychotics to get FDA approvals for kids.

I wish I could make this clearer, but I'm still recovering from my recent bout with death.  There's no science here, only a tinkering with language and loyalties, with staggering results.  Don't blame Pharma quite yet-- this is a NIMH study.

I am not against antipsychotics, and I have long tried to tell anyone who would listen that the data clearly show they are superior to antiepileptics.  But this isn't psychiatry suddenly waking from a coma, aha! it turns out the existing data do show antipsychotics are mood stabilizers!    Instead of using them to replace antiepileptics, they will use them to replace everything: SSRIs, benzos, antiepileptics, stimulants, etc. 

And polypharmacy will only be reincarnated-- in the form of multiple simultaneous antipsychotics (Abiliquel, anyone?), with preposterous pharmacologic justifications ("this one acts on serotonin, so it's the antidepressant, and this one on dopamine, so it's the antimanic.")   If anyone says that to you, stab them.

You don't get many changes like this, maybe once every ten years-- the last was the beginning of the Depakote era, and before that was the advent of SSRIs, each with it's own erroneous semantics ("kindling model;" "serotonin model of depression.")

I wish all the patients in the world good luck, you'll need it.  Not because of the antipsychotics themselves, which will work or not, oblivious to doctor and diagnosis; but because of the doctors, who take little interest in examining the evidence behind their practice, and even less interest in reevaluating its core principles; and who lack the courage to even treat what they see, instead resorting to artificial, and wrong, paradigms and algorithms.  There's not even pseudoscience here.  Psychiatry is being lead by the siren call of semiotics, and it is saying, follow me, I am made of words...







Comments

My first clinical superviso... (Below threshold)

April 6, 2007 8:20 AM | Posted by Cheryl Fuller, Ph.D.: | Reply

My first clinical supervisor told me that we practice what we believe. Which is corollary to your Psychiatry is not about science, it is about language, politics.

And imagine the results should a serious study be made of placebos and the good response to them that we see in so many studies!

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I'm very much in agreement ... (Below threshold)

April 7, 2007 6:58 PM | Posted by Dr DJ: | Reply

I'm very much in agreement of your article. Inbetween the almost daily laments of how much it sucks to work in an ever-crumbling NHS, those amongst us who're more stuck in their ways are vocally resisting this new trend. I've read a number of patient leaflets, presentations and drug rep freebie textbooks recently that advocates standard treatment for BPD as mood stabilizer plus antipsychotic. You're right, this is all about politics and the power of words and not science. Reading your post reminded me of a very eloquent article by Prof. Healy I read a while ago on a similar theme.

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"kindling model"No... (Below threshold)

April 9, 2007 1:55 AM | Posted by Short Talk: | Reply

"kindling model"

Now that was a piece of nonense. Essentially it tried to claim that the behaviour causes the behaviour. A specious bit of acausal illogic that turns up regularly in psychiatry. Behaviour doesn't occur in the absence of perpetuating factors (beyond the behavour itself).


"Psychiatry is being lead by the siren call of semiotics, and it is saying, follow me, I am made of words..."

A view I have held for a long time. Frankly, the way psych is going it won't exist in 2-3 decades.


And thanks, Dr DJ, for the Healy article link.


All this reminds of the old advice given to trainee psychs: Use new therapies quickly, before they lose their effectiveness (ie before the placebo effect wears off and the patient community wises up).

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I've been delighted that on... (Below threshold)

April 9, 2007 6:55 AM | Posted by Nancy Lebovitz: | Reply

I've been delighted that one of my friends who was getting pretty bad results on anti-depressants is now stable and happy being treated for Bipolar 2, but I bet I wasn't cynical enough--I expect you're right that we'll see people who are depressed getting inappropriate treatment for bipolar.

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Hello there!!!Very... (Below threshold)

April 9, 2007 7:03 AM | Posted by Health Watch Center: | Reply

Hello there!!!

Very interesting post and article...thanks for sharing...you have nice blog with helpful information...well I came across to you blog while was searching for depression blogs and have found resourceful...great job keep the good work going...

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STEP-BD and the Sachs study... (Below threshold)

April 9, 2007 7:17 AM | Posted by Charles: | Reply

STEP-BD and the Sachs study appear to be valid attempts to understand what works and what doesn't work in the treatment of bipolar disorder. The contribution of antipsychotic drugs to the results is likely to be small, since according to Figure 1 in the NEJM article, less that 10% of subjects were taking this class of drug. The majority were taking lithium or valproate. So I'm not entirely clear why you suggest that this study will herald a new age of increasing use of antipsychotic drugs for the treatment of BPD?

Of relevance to this topic, I attended a debate held by the International Review of Bipolar Disorders last year entitled "Are atypicals preferable to mood stabilisers for symptomatic treatment in bipolar disorder" chaired by two European psychiatrists, Erfurth and Grunze. In this context, mood stabiliser refered to lithium, valproate, lamotrigine etc. The final vote was clearly in favour of the mood stabilisers over the atypicals.

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Hi, did you receive my comm... (Below threshold)

April 11, 2007 1:32 PM | Posted by Charles: | Reply

Hi, did you receive my comment the other day? I was asking whether you thought that the Sachs study, including just 10% per group of subjects on atypicals, was really saying much about the role of this class of drug in the treatment of bipolar depression?

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I have an old friend I don'... (Below threshold)

April 11, 2007 8:28 PM | Posted by anonymous: | Reply

I have an old friend I don't talk to often who is a Lilly rep, and in her "expert" opinion anyone with bipolar should be on an atypical (preferably zyprexa of course) period. She honestly believes this and, according to her, has convinced many/most of the docs she details that zyprexa should be first line for anyone with mania or a history of mania. I knew there was a reason we weren't that close!

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What about lamictal?<... (Below threshold)

April 13, 2007 7:26 PM | Posted by connie: | Reply

What about lamictal?

I take it for bipolar type two. Pity the fool that tries to give me anything else. And believe me, I'd been put on just about everything before I tried it.

Five years later it still works.

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Right on time:<a hre... (Below threshold) I would argue that as alway... (Below threshold)

April 14, 2007 3:57 PM | Posted by CPP: | Reply

I would argue that as always, capitalism takes every opportunity to exploit progress. While there are continual refinements in our diagnostic ability, the rush to fill the therapeutic vacuum is often prematurely filled by what already exists wrapped in a new package. Don't dismiss what is actual evolution of our diagnostic ability because the hucksters are climbing over each other to offer the next best treatment (which they happen to sell).

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1)Behaviors do cause... (Below threshold)

May 17, 2007 4:33 PM | Posted by Driving Miss Delusional: | Reply

1)Behaviors do cause behaviors. Not so much psychoses, mania, depression, and such- but these aren't behaviors. Destructive coping mechanisms, on the other hand, are entirely self-propogating.

2)Remarketing expensive drugs still under patent to patients who've had their dxes manipulated enough to justify relentless pursuit of a mood-stabilizer certainly isn't new. Is it the monotherapy aspect that's revolutionary here?

This is disturbing, but not at all surprising. There is a reason SSRIs have enjoyed such wild popularity. People actually suffer from major depressive episodes, some of us repeatedly throughout life. The drugs of the 80s and 90s are integral to our well-being. I, for one, react pretty poorly to drugs with as heavy a load of depressant effects as are most anti-psychotics.

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Was reading about psychiatr... (Below threshold)

August 21, 2007 12:47 PM | Posted by data010101: | Reply

Was reading about psychiatry as a science: Agree - I describe my bipolar as a "neurological situation", therefore I would seek a neurologist. Bipolar for me is best described with pain language. Pain drugs are used for depression? Heroin for the blues? I have a VNS implant - seems to work for depression, not anxiety or mania. So whatever electricity does for my brain - I don't care, seems to work. VNS contraindicated for bipolar - go figure! So it's indicated for depression? The scientific task is complicated, and I'd much rather have it in the hands of research scientists than psychiatrists or New Age mumbo-jumbo people. My wiring is goofy - whether genetic or the result of viral infection, my brain "lights up" differently from a lot of other people, making my existance painful to myself and others at times.

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As someone with strong obse... (Below threshold)

January 27, 2008 1:37 PM | Posted by Hiding: | Reply

As someone with strong obsessional sx, the whole "Now it's not depression, it's BIPOLAR!" is a great focus for my obsessions. I am treated for depression and anxiety -- and {ahem} everybody knows that depression and anxiety together are "really" bipolar, right?

So add another to my list of obsessions: "Uh oh, I'm feeling especially talkative today -- does that mean it really is bipolar?" "I'm so irritable with my husband today -- is that a sign it's really bipolar?" (Never mind that my husband is a carrier for irritability some days...)

Of course, I have an anxiety disorder, so I react to the thought of a different dx with -- anxiety. (I haven't responded well to most of the antidepressants or anxiolytics I've taken, so the part about having to change or add medications is a reasonable reaction.)

Fortunately, I now have a really wonderful psychopharmacologist who believes in really weird, fringe style theories -- such as the one that says a person can legitimately have both 296.33 AND 300.00 at the very same time without necessarily being bipolar.

For what it's worth -- I consider this particular obsession iatragenic.

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99% of what you predicted h... (Below threshold)

October 6, 2010 5:48 PM | Posted by skeptic: | Reply

99% of what you predicted has become true.
'short talk' commented that the remaining life of psychiatry is 10-20 yrs.
There are elaborate advertisements for scientology on TV now!

There are only 4 medicines in psychiatry: imipramine, chlorpromazine, diazepam, lithium. Lithium is debatable. I had teachers who basically practiced with h
aloperidol/trifluperazine/chlorpromazine, diazepam, imipramine.

Chlorpromazine hits everything and so does seroquel. We are back to the 50s.

There was also ECT which is still there but chained, tamed to the cell of depression.

There is a limit to what you can do by tinkering with hardware. That limit was reached 50 yrs ago. There are no easy, reliable, software fixes which will work for a majority. But most should be able to find some software fix that works for them.

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so good .Thanks for the inf... (Below threshold)

October 9, 2010 5:17 AM | Posted by iPhone Cases: | Reply

so good .Thanks for the information you post.
Thanks for posting this.iPhone Cases

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Having just hade my first m... (Below threshold)

December 21, 2012 9:56 AM | Posted by Jens: | Reply

Having just hade my first meeting with your blog, I am fascinated. Don't have any academic experience of psychiatry, but I'm diagnosed with borderline. I'm 33 now, but got my diagnosis just 3 years ago.

The psychiatrist I was seeing as I first got in contact with psychiatric care ("the carousel", many people call it here in Sweden)thought I was bipolar (type 2). The only reason I can see for her assuming this is that my down periods usually didn't last very long. Have I misunderstood what I see and hear, or is bipolarity "the new thing"?

Kindest regards from snowy Stockholm,

J

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So, 7 years later, what of ... (Below threshold)

November 19, 2014 5:17 AM | Posted by Otto: | Reply

So, 7 years later, what of your predictions?

I am not a psych academic, just a psych med facilities attendant diagnosed with borderline pers disorder.
I think that for a lot of people looking through the Internet for infos about their psych problems, it would be great to have an update at the end of the article, or a final comment, to tell how much the predication was right or not.

regards,
otto

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It would be neat to connect... (Below threshold)

November 19, 2014 11:12 AM | Posted by : | Reply

It would be neat to connect my IPV6 refrigerator to the router through electric cables. I don't fully trust wireless to be healthy.

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