Arkansas Unleashes The Razorbacks on Risperdal

As documented at Furious Seasons, the state of Arkansas has leveled some very serious allegations at Johnson & Johnson, manufacturer of Risperdal via its subsidiary Janssen. Furious Seasons was kind enough to post a copy of the lawsuit. Here's a partial listing of the allegations:

• J & J hid the extrapyramidal side effects of the medication through conducting scientifically bogus studies which covered up the risks of Risperdal
• J & J marketed Risperdal off-label for such conditions as ADHD, depression, anxiety, and aggression associated with dementia
  
• J & J falsely represented Risperdal as cheaper and more effective than older antipsychotics
• J & J did not represent their own knowledge that Risperdal is associated with weight gain
• J & J offered kickbacks to physicians to prescribe Risperdal for "non-medically necessary" uses

The lawsuit makes for interesting and inflammatory reading. Keep a couple of things in mind when considering these charges

• Zyprexa was clearly marketed off-label for various conditions (1, 2, 3)
  
• It seems that Lilly was involved in hiding the risks associated with Zyprexa (1, 2)
  
• Bristol-Myers Squibb just settled a large lawsuit, partially regarding claims that it promoted Abilify off-label
• Take a look at a couple studies (1, 2) that were designed to encourage off-label prescription of antipsychotics as well as a "scientific review" of relevant literature on antipsychotic off-label use.
• And of course, there are several states (I've lost count of exactly how many) that are suing Lilly for its promotion of Zyprexa and its alleged concealment of risks associated with the drug.
  

I don't know about you, but I think I'm seeing a pattern emerging here. And while we're talking about weight gain, diabetes and the like, I hope you all have a fantastic Thanksgiving.

Lilly Updates Label: A Little Too Late

The good news is that Lilly has updated its warnings for Zyprexa (olanzapine) and Symbyax (olanzapine/fluoxetine combo). Here's a bit from the PR release:

Specifically, the changes include new warnings for weight gain and hyperlipidemia (elevation of triglycerides and cholesterol) and updated information in the warning for hyperglycemia (elevated blood sugar), including additional language on a greater association of increases in glucose levels with olanzapine than with some other atypical antipsychotics.

Here's the tragicomic part:

"Today's communication is part of Lilly's historical and ongoing commitment to inform doctors and patients about updated prescribing information," said Sara Corya, M.D., global medical director, Lilly.

AND

"Lilly continues to recommend that clinicians consult expert guidelines for treating people with antipsychotics, particularly the monitoring of lipids and blood glucose, regardless of the medication prescribed," Dr. Corya said. "Over the last several years, the company has been actively informing healthcare professionals about these recommendations."

Yes, Lilly is all about honestly sharing information. Please read my prior post on the incredible shifting Zyprexa glucose data here. Read a whale of a great post from Furious Seasons on how Lilly tried to play weight gain on Zyprexa off as a benefit of treatment (!) here. Interesting questions about Lilly's handling of the glucose discussion can also be seen here. If you have some time to burn, look through the above posts, then tell me Lilly has a "historical and ongoing commitment" to sharing data openly and honestly.

As for the expert guidelines, yeah -- great idea! Like TMAP -- read my postabout how the research supporting said guidelines for treating bipolar disorder is flimsy at best, yet these "expert guidelines" are oft-cited as a great example of the good that comes from expert guidelines. Oh, and did I mention that the "expert guidelines" are often authored with the help of industry?

Here's the bad news. Really bad news. Philip Dawdy has posted an interview with the mother of a man who took Zyprexa, apparently piled on the pounds, and then allegedly died of "profound hyperglycemia." It is a sad, sad story and well worth your time to read it.

While you're there, look around the Furious Seasons blog and ask yourself, "Is there anywhere else where I can find this type of mental health coverage?" I bet you'll say no. If you want continuing coverage of these issues, I suggest that you contribute whatever you can to Philip Dawdy, author of Furious Seasons.

Zyprexa for Teen Bipolar

Zyprexa for teen mania is great, except for the Fat Camp Factor -- from the study abstract:

The mean baseline-to-endpoint weight change was significantly greater for patients receiving olanzapine relative to patients receiving placebo (3.7 kg versus 0.3 kg), and the incidence of treatment-emergent weight gain 7% of baseline was higher for olanzapine-treated patients (41.9% versus 1.9%)

The drug did appear to be much more effective than placebo according to the abstract, but I'll have to read the article before I can weigh in on efficacy more confidently. Gaining 7% of your body weight in three weeks? Um, that ain't good. Gimme a D, Gimme an I, Gimme an A (can you see where I'm going here -- diabetes, anyone?)...

Maybe these kids should have been drinking diet soda -- that will save them from weight gain, at least that's what Lilly might tell them. There were 13 "authors" on the study -- apparently being good at recruiting patients counts as authorship, since there is no way that 13 people made a legit contribution to the study outside if recruitment is left out.

More at Furious Seasons.

Dawdy Podcast Now Available

You can now listen to the All in the Mind broadcast featuring Philip Dawdy as well as a Lilly spokesperson here. I only caught half of the broadcast yesterday. I'll save my full review of the broadcast until I've heard the full show, but I do feel comfortable saying the following...

The Lilly spokesperson deserves a large salary -- no, make that an enormous salary. His take of blaming mental illness for health problems, while giving Zyprexa a free pass, appears to be a significant detour from reality (1, 2, 3). To make the statements he made while sounding sincere -- well, that deserves applause. I doubt most people could pull off such a performance.

Most folks don't have time to run through the full text of a bunch of journal articles. Here's the quick way to briefly review the current research on the topic of Zyprexa and diabetes. Go to PubMed. Type in olanzapine and diabetes and then read the abstracts of the articles that emerge. Then tell me with a straight face that olanzapine is not related to health problems.

Zyprexa Does Not Cause Diabetes?

That's not what one set of physicians believe, despite Lilly's protestations to the contrary. Here's what they recently reported regarding one case:

The authors report a case with life-threatening hyperglycemia and acidosis in a patient with no previous diabetic history following treatment with olanzapine. A 35-year-old woman with a history of bipolar affective disorder treated with olanzapine presented with severe diabetic ketoacidosis. She had no prior history of diabetes or risk factors for diabetes. Glycosylated hemoglobin (HbA1c) on admission blood sample suggested that long-term glycemic control had been poor. The authors postulate that treatment with olanzapine precipitated hyperglycemia, an elevated creatine kinase level, and a high amylase level.

Perhaps someone should have told these physicians that Zyprexa is a safe, gentle psychotropic that could not possibly induce such nasty side effects.

Glucose and Zyprexa

Increased glucose levels are generally considered a risk factor for diabetes. Thus, there has been some concern that olanzapine (Zyprexa) may increase glucose levels, which may relate to the increase in diabetes incidence among users of Zyprexa. Glucose is not the only risk factor for diabetes, but it is generally a concern if a medication tends to increase glucose levels.

The following is some rewording and summarizing of Furious Seasons' recent post on one document related to the Zyprexa-glucose issue:

Lilly had some data indicating that patients who took olanzapine plus mood stabilizers had a mean increase in glucose levels while patients who took placebo plus mood stabilizers showed, on average, a mean decrease in glucose levels.

Dr. Mauricio Tohen of Harvard/Lilly (interesting combination) said that he would like to include the above information when discussing Zyprexa data because he said that the glucose increase was reversible. However, another Lilly official pointed out that since Lilly is aiming for long-term treatment with Zyprexa, pointing out that glucose increases can be reversed when the drug is discontinued does not make much sense. Good point: If the drug has a side effect that can be reversed if you stop taking it, don't tell anyone -- they might not take your drug in the first place!

I'd be interested in tracking down what exactly happened to this data, including whether it ended up hitting the scientific literature in a manner that was accurate, or whether the glucose issue was swept under the carpet. More to come on this one if I can successfully dig up more information.

Mega hat tip to Furious Seasons, who continues his excellent reporting on all things psychiatric, with a special focus on bipolar disorder, schizophrenia, and pharma. I strongly encourage all to read his post on glucose and Zyprexa here.