Seroquel Wants You!

Last weekend, I referred to a few studies that have popped-up on the use of Seroquel in bipolars. It was a study sponsored by the makers of Seroquel, AstraZeneca. AZ is one of the largest pharma companies in the world. Of late, they have been on a real marketing blitz with Seroquel. There's a story in that and a history lesson.

The drug was first developed and marketed for schizophrenia. Patients with that disease had pretty good responses to the compound, as they did with other atypicals. We're not talking complete symptom remission there so much as we are talking about be able to control the nasty aspects of schizophrenia--it can knock down the wildness and raging quite well, as well as hallucinations and paranoia--without the unacceptable side effects of what docs politely call movement disorders (ie, zombieism) that are part and parcel of treatment with older "conventional" antipsychotics. Atypicals have different side-effects, as I've noted throughout this blog. But they are a bit easier for patients to bear in the short-term. (I think docs are only now starting to wake up to these newer side effects. But I'll write about that in another post.)

Then, docs began to use atypicals casually to go after the manic end of bipolar disorder. The APs were not yet licensed by the FDA to be used that way--we're talking 1999 and 2000 here--but docs were getting a wee bit desperate for ways to address mania. Previously, bipolar had largely been treated with a combination of a mood stabilizer (most commonly, Lithium, Depakote--valproate/valproic acid in its recently available generic forms--and Lamictal and other anti-convulsants) and an anti-depressant (you know the names of these!). These meds can be pretty damn useful in long-term management of bipolar, especially the mood stabilizers. Anti-depressants are a somewhat dicier proposition, as is well-known by bipolars and depressives the world over. (After all, why would Wellbutrin's maker run television ads bluntly touting that anti-d's decreased sexual side effects if there weren't serious issues in other anti-ds?)

But many bipolars have problems with mania, in its extreme and mellower forms, despite taking 2500 mgs. of Deapkote a day. How many bipolars were having such problems? Hard to say. No one I've run into in the research world will hazard a guess. It must be a fairly large subset of bipolars, however, because as docs began to prescribe atypicals to bipolars in 2000, 2001 and 2002, sales of atypicals exploded. The companies and the meds had already hit their sales ceiling of about $4 billion in the schizophrenic market. Once docs began to see robust responses to atypicals such as Zyprexa, Risperdal and, then, Seroquel in patients, the word got around the psych community that if you had a bipolar whose mania was breaking through more conventional therapy, then give these atypicals a whirl. Apparently, there was, and is, a lot of whirling going on. In 2004, sales of atypicals hit $9 billion.

By then, most of the atypicals had been licensed by the FDA for use in acute mania. Pharma companies made their case to the FDA by sponsoring short-term--typically 8 to 12 week--studies of bipolars with acute mania taking atypical X versus placebo. The studies were performed academic clinical settings by various psych researchers. Clinical studies typically involve the following demographic, according to NIMH documents I've reviewed: males and females aged 30 to 45 without substance abuse problems or other underlying health concerns (ie, cardio-respiratory, etc.). Typically, study subjects are white. (cf., NIMH's "Strategic Plan for Mood Disorders," in which the top dogs at our primary research agency bitched at length about the lack of diversity in study subjects--an extremely apt bitch.) Suffice to say, that clinical academic settings barely approximate the real world. Such settings are great for basic efficacy trials. As of now, there are NO studies of long-term, much less medium-term, use of APs in bipolars. Nonetheless, these short-term studies and the anecdotal experience of docs in private practice--and multiple visits from friendly phrama sales reps!!--drove the rapid acceptance of APs in bipolars.

The first long-term study of the use of atypicals in schizophrenics came out in September. It's called the CATIE study. It wasn't a resounding victory for anyone, especially the patients. I have posted on this elsewhere in this blog. The second round of results from this study will be published in March 2006. I can't wait.

Just how applicable is the experience of schizophrenics to bipolars? In recent weeks, researchers and advocates I have spoken with have chided me for even asking whether the evidence from CATIE means anything for bipolars because the evidence pointing to bpers have a similarly rough go with the APs is anecdotal. While I understand their objection in a scientific sense (you can't do confidence-interval stats in an anecdotal world), I think they ignore the experience of patients in the real world at their, and their patients', peril.

After all, atypicals target the same receptor in the brains of bpers as they do with schizophrenics--ie, the dopamine receptor. The APs are the same molecules in bpers as they are in schizophrenics. The meds operate in the same human physiology. They are chasing the same basic behavioral issues. All of these are facts.

For anyone to claim that there isn't a pretty strong correlation between experiences--especially the physical side effects ones--of schizophrenics and bipolars on these meds is stupid. I don't argue that there is a 1:1 correlation, but I'll bet my life savings on it being about .8:1, or 80 percent. Besides, asking patients to take APs for long-term maintenance--as opposed to the short term wonderland of clinical studies--without having the long-term studies to back up that approach is flat out arrogant and disrespects the rights and valid experiences of patients in the real world. As far as I know, we are the ones paying the freight around here.

Such a mindset among clinical researchers also evades the basic fact that atypicals--all of them!!!!--now carry a BLACK BOX on their labels. Meaning: Use with caution. Can cause elevated sugar levels and so on.

So why am I popping off on this basic theme again? Because, as I mentioned at the top, this study came out showing that Seroquel can be used to treat what's known as bipolar depression. That's, of course, the bad dark end of bipolar disorder. Lots of patients have a tough go with that--I have--and a lot of bipolars have a tough time sticking with anti-ds. Anti-ds aren't exactly seamless--as noted above--and truly work for 50 percent or fewer of the people who take them. And so the AP makers are trying to get their products FDA-approved or treating bipolar depression. That way, they can loose their sales reps on psych docs to claim that "Hey, you can use this med for the depressive end of bipolar disorder, too!"

Depending on whose numbers you believe, there are anywhere from 2.3 million to 8 million bipolars in America (I'll discuss these numbers another day). I've never found an estimate of how much a slice of the psych meds market we are, but I wouldn't be shocked if we were about one-third. So of course pharma companies want to market to us!

AstraZeneca put out a raft of press releases on that paper, trumpeting the results. It was recently picked up by a television news broadcast in Austin, Texas, and likely by other stations as well. Please read the web copy to see what you think of that. The limited point I'll make about broadcast news picking up the story--no matter how small the coverage--is that it's only presented in terms of bipolars need meds and meds only. At $400 a month. They never discuss side effects or what it's like taking these meds long-term. That's unfair to viewers and psych patients. (I'll take up the media and psych meds as a long post some other day.) I am officially pooped--and it's sunny out.