E-Mail: AstraZeneca Knew in 1997 that Seroquel Caused Weight Gain

Last Updated Mar 3, 2009 2:40 PM EST

AstraZeneca knew as far back as 1997 that Seroquel put patients at risk of weight gain, according to the company's own internal memos. The documents also appear to show that some AZ execs developed strategies to "neutralize" information that suggested Seroquel caused weight gain or diabetes, even after the FDA asked the company to warn patients about Seroquel's diabetes side effect.

The memos were produced in the ongoing Seroquel litigation. The contents of some of them have been reported on before, but Philip Dawdy at Furious Seasons has created a page on which they can all be downloaded, here.

The documents consist of AZ's internal emails, draft papers and promo materials. Some of them concentrate on whether the data on Seroquel was showing signs of weight gain or diabetes. And the Clinical Psychology and Psychiatry blog has a lengthy dissection of just one study that seems to show that Seroquel isn't as good as Haldol. What follows, however, is a selection of quotes from memos written by AZ's staff, all on the subject of weight gain, diabetes, and whether the company knew that Seroquel was causing these side effects. The memos form a timeline of who knew what, and when.

Feb 12, 1997, memo from Richard Lawrence: I am not 100% comfortable with this data being made publically available at the present time ... however I understand we have little choice ... Lisa has done a great 'smoke-and-mirrors' job!

Aug. 13, 1997, memo from Lisa Arvanitis to her colleagues: 1. Is there a competitive advantage for SEROQUEL re-weight gain which we can articulate in posters/talks/vis aids? We know we have weight gain but is it limited to the short term ...? ... I was really struck by how consistent the data was.

Feb 24, 1999, memo from Nick Hough, regarding a single study that appeared to find weight loss among users: We must not get too carried away with 'weight loss' when we know the rest of our data appears to point in the other direction...

Dec. 6, 1999, email from John Tumas: The larger issue is how do we face the outside world when they begin criticizing us for suppressing data.

1998 draft paper intended for 11th ECNP conference in Paris: Clinically significant weight gain, that is more than 7 percent increase in body weight, was seen more with quetiapine [Seroquel] than placebo - 24 percent compared with four percent ...

Clin Drug Invest Journal, Aug 18, 1998, Zeneca sponsored study, "Effect of Clozapine-Quetiapine Combination Therapy on Weight and Glycaemic Control": All 65 patients showed weight loss ...

2000 study in International Journal of Psychiatry in Clinical Practice, written by AZ: In these patients, there was no overall effect on weight across the body mass index ...

March 23, 2000, memo from John Tumas: The data don't look good. In fact, I don't know how we can get a paper out of this.

June 22, 2000, discussion document: Safety data ... suggest the possibility of an association between SEROQUEL use and impaired glucose regulation including reports of new onset diabetes mellitus... the number of reports is fairly sizeable.

August 2000 memo from AZ to the FDA: Thus very few cases of diabetes mellitus (and related complications), hyperglycaemia, and weight gain have been reported. AstraZeneca believes that the current US Seroquel label accurately describes patient experiences to date of these conditions.

Oct. 26, 2000, memo from Dominic Aked: I agree we need to be able to tell a convincing story to our internal and external customers. I'm sure we can do this...A promotional claim 'Seroquel is weight neutral during the long-term treatment['] should help make this distinction.

[By July 2001, AZ had received at least 46 reports of diabetes in patients taking Seroquel, 21 cases of ketoacidosis or acidosis, and 11 deaths. By the end of 2003 AZ had received at least 23 more.]
Headline on promotional piece with a 2001 copyright: Distinct advantages of a favorable weight profile

Sept. 15, 2002, FDA letter requiring label changes re diabetes: ...we have concluded that the product labelling for all atypical antipsychotics should be updated...

Nov. 26, 2002, "Objection handler" for sales reps: The company's safety database has reassuring data concerning Seroquel's diabetic potential...

[The FDA asked AZ to send out a dear doctor letter about diabetes and Seroquel on Sept. 11, 2003. AZ did not send out the letter until January 2004.] March 4, 2003: Sales rep detail flow: Key Communications: Seroquel, unlike some other antipsychotics, is not associated with meaningful weight gain, either in the short or long term or across the recommended dosing range. Oct. 15, 2003, memo from Russell Katz to FDA: AstraZeneca completed a comprehensive internal analysis of existing data and concluded that the available data do not establish a causal link between diabetes and Seroquel.

[On April 24, 2004, AZ was forced to send out a revised "Dear Doctor" letter due to the fact that the first one was misleading, as it potentially downplayed the need to continually monitor a patient's blood sugar levels.]
"VM 08 15 05" Our objective is to neutralize customer objections to SEROQUEL's weight and diabetes profile.

Nov. 16, 2006, FDA writes a 'Warning Letter' regarding a sales aid: This piece is false or misleading because it minimizes the risk of hyperglycaemia and diabetes mellitus ...

Dec. 18, 2008, memo from FDA: The weight gain signal is significant for both adult and pediatric populations and should be elevated to the Warnings and Precautions section [of the drug's label].