thelastpsychiatrist.com - Atypicals for Maintenance Bipolar. Adnotated.

In my post on the NEJM article about antidepressants in bipolar depression, some people couldn't see how I made the leap to a political movement away from SSRIs and seizure drugs, and towards atypicals.
First, I'm not against atypicals. I have long advocated for fluctuating doses of antipsychotic instead of Depakote.ⁱ I do think they can treat depressive states. I don't disagree with the study or the data.

What I find perplexing is the timing. I was trying to show how academic psychiatry has now decided to move towards atypicals. Why now?

Here's an example. Eduard Vieta just released his hit single, Current Approaches to the Treatment of Bipolar Disorder With Atypical Antipsychotics, in Primary Psychiatry. In it, there is only one short paragraph on Depakote, describing its one maintenance study, in which (it states correctly) Depakote didn't beat placebo. That's it. 81 words.
Find me one other article written before 2007 that is so curt and dismissive of Depakote.

It goes on to explore the data on atypicals -- and there's quite a bit. It rightfully concludes, "atypical antipsychotics have shown promising results in bipolar disorder maintenance therapy."

But here's the point: with two exceptions, all studies on atypicals referenced here came from 2004 and earlier. The two exceptions were from 2005.

So it's not new data, it's old data. Did they suddenly read the back issues?ⁱⁱ Holy crap, atypicals might work? That's why that NEJM piece is so important. It marks the point where academia has decided to embrace atypicals and move away from Depakote. If this move was really data driven, they would have done it in 2004. Hell, they would have done it in 2001 when the Depakote maintenance study didn't beat placebo.

There's no conspiracy here, there's no exploitation of the weak for personal profit. I'm not saying these are bad people, not at all. They are not conscious of it. That's what makes this politics, not science.
You have an academic career, you want to do clinical research, who's going to pay? NIH money is hard to get.

So you turn to Pharma. You "get" to do a clinical trial of Depakote for the treatment of bipolar. When you're done, maybe they hire you to do another one.

You, personally, don't even get the money -- the department does, and they use it to pay your already set salary. But you get a career, an identity. But you start to believe the prejudices of your chosen stomping grounds, and ignore the shortcomings. You become a nationalist.ⁱⁱⁱ You start to believe that Depakote is first line, despite data; or that all seizure drugs will work; or that this thing you called bipolar is actually what you're treating. That there are actually two poles.

Then the money dries up. But Abilify says, could you do a clinical trial of Abilify for bipolar? And you say, sure, why not? maybe Abilify could be an add-on? And then it's monotherapy^iv. And then Seroquel funds a study.

The last part is when you don't simply move on from Depakote -- you distance yourself from it. "You know, its data was never that great, it was really just an antimanic, and anyway, it had horrible side effects." It's the next step of political hypocrisy: I was never really a citizen of that nation, I have really always been a citizen of the world.^v

1. Valproate is quite possibly the driver behind the "autism epidemic", so by all means, anything but Depakote's a good idea. [↩]
2. This is not even improbable. Have you read all of Trilema ?

   And understood what it says ?

   Three-four years, which is the time window contemplated here, is certainly not so long an interval as to put much bite behind his diss. Indeed they very well might've just now read the back issues. [↩]

3. This is how paradigms work in science in the first place ; and there's excellent reason for their existence, too (in a few words : that they permit a complex issue to be narrowed enough so some actually productive work may be done, instead of spending whole life paralytically gazing at the starry sky). Someone might benefit from reading a little theory of knowledge / history of science I'd say. [↩]
4. What he means is, "and then Abilify becomes the only drug to use". [↩]
5. This is how females throughout history survived long enough for there to even be a species in the first place, you know ?

   Do you know ? Model, for curiosity's sake, what happens if every time tribe A defeats tribe B, the female portion of tribe B goes down with the ship. Ready ?

   So there's 100 tribes, and they are normally distributed between 100 and 10`000 members. Every generation each female has four boys and five girls, and there's a major war, pitting 1/3 of the tribes against each other, in random pairings. Every time a tribe reaches 10`000 females it splits into two tribes, one carrying 2/3 of the males and 1/3 of the females and the other carrying the rest ; every time a tribe reaches 0 females it disappears.

   Do you see how if the result of conflict is "all the males are killed", the population stays on a slow but stable growth pattern exactly matching historical record whereas if "all members are killed" the population dwindles to nothing within a dozen generations, or do you have to actually run the numbers ?

   Loyalty in the sense here contemplated was mostly bred out of females before writing was a thing. The pressure's there, and in evolutionary terms the prize for dying early is... not being represented downstream. The deep reason for "not asking the woman anything" as the central pillar of human sexual activity has nothing to do with contempt, and everything to do with historical reality : what the fuck was she going to say anyway ? [↩]