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...