Demented Marketing of Zyprexa?

Background: There has been prior mention of how Zyprexa was allegedly marketed off-label as a treatment for dementia, including writing by Alex Berenson. This post will provide more details regarding this issue, especially about the hypothetical case of “Martha,” a case used by Lilly sales representatives in their meetings with physicians.

Before reading this piece, please note that Lilly has denied that it markets its products off label.

Martha’s symptoms have been described as much more strongly resembling dementia than either schizophrenia or bipolar, the only two indications for which Zyprexa is FDA approved. According to Alex Berenson, Martha was described as

a widow with adult children "who lives independently and has been your patient for some time." Martha was described as being agitated and having disturbed sleep, but without the symptoms of paranoia or mania that typically marked a person with schizophrenia or bipolar disorder.

Berenson noted that a Lilly spokesperson said that Martha was intended to represent a patient with schizophrenia.

More on Martha: Here is more on Martha, perhaps from the same document examined by Berenson. This document is titled Zyprexa® (olanzapine) Primary Care Q3 Implementation Guide, and it is dated June 2001.

This is Martha. Martha is a widow who lives independently and has been your patient for some time. She is becoming more complicated to manage, and you note increasing agitation. Her sleep is disturbed; she dozes during the day and is up most of the night. Her family has shared their concerns with you, saying, “She thinks we’re trying to take advantage of her.”

Martha’s family doesn’t want to send her to a nursing home, but her agitation and confusion must be addressed. Your goals of treatment for Martha may include reducing her behavioral disturbances without impairing her cognitive functioning.

Does Martha Have Schizophrenia? Upon checking the Diagnostic and Statistical Manual for Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria for schizophrenia, it appears that Martha does not meet the diagnostic criteria for schizophrenia, despite Lilly’s claims that Martha was intended to represent a patient with schizophrenia.

Later, the same document discusses possible Zyprexa dosage for Martha.

…a starting dose of 5mg – or even 2.5 mg – at bedtime is appropriate.

In schizophrenia trials, Zyprexa is typically dosed at 10-20 mg, not 2.5 mg-5 mg. This also apparently contradicts Lilly’s claim that it was intending Martha to represent a patient with schizophrenia, as it would make little sense for Lilly to recommend a subtherapeutic dose of Zyprexa to physicians.

Under the heading of Back Cover/Close, it is stated:

In summary, doctor, prescribing ZYPREXA is a safe, proven solution for patients like Martha/Michael/Kelly who suffer with mood, thought, and behavioral disturbances. It’s easy to use, and it works [emphasis in original].

Again, note the broad terminology. Rather than discussing bipolar disorder or schizophrenia, for which Zyprexa is indicated, the language of “mood, thought, and behavioral disturbances” is in place, which suggests much a broader application of Zyprexa.

In the same document, a potential question that reps may receive from doctors is mentioned:

With Martha I would just prescribe a cholinesterase inhibitor, such as Aricept. They are supposed to be pretty good with agitation.

Rep: …Why not prescribe ZYPREXA, which has proven efficacy for agitation and related behavioral disturbances [my emphasis], has been on the market for more than 4 years, and has helped over 6 million patients with symptoms just like Martha’s?

In the case of Martha, note again that schizophrenia is not mentioned; instead, “agitation and related behavioral disturbances” are brought to the fore.

FDA Indication for Dementia? In the same document, under the heading of “Helpful Hints,” subheading titled “Martha Spread,” it is stated that

…You will note that on the right-hand side of the spread under the cognition information is a space that has been intentionally left open. Upon launch of the IM [intramuscular] formulation of ZYPREXA, we will be placing a sticker in this spot to announce the new formulation and new indication (agitation associated with dementia) [my emphasis].

Zyprexa was never approved by the FDA for the treatment of dementia, though it would appear from the above quote that Lilly was expecting such approval.

Email Message: To shed further light on the possible off-label promotion of Zyprexa for dementia, further documents were reviewed, including an email issued to “Area Zyprexa Champions,”

Since the diagnosis of our 3 patients in the Zyprexa core message piece are: Martha – dementia,[my emphasis]…can you enlighten us a little more about dementia. We know that we are to describe the symptoms and stay away from diagnoses, but for our own background, can you elaborate on dementia…We are getting a little grief from some of our docs about promoting Zyprexa for dementia [my emphasis], but according to the slides in the audioconference set, there is no FDA approved drug for dementia.

This email clearly indicates that at least some individuals at Lilly were seeing Martha as a case of dementia and that some doctors seemed upset about Zyprexa being promoted for dementia.

Martha’s Symptoms Increase as She Ages: Another document, titled Zyprexa Retail Implementation Guide states under the heading Sales Call, subheading Patient Profile

Martha is a widow you’ve known and treated for several years. As she’s aged, she’s become more complicated to manage – clinically, and at home. These are comments you hear from her family (read testimonials from profile). Your main goal of treatment is to treat her illness and reduce her behavioral disturbances. Do you see patients like Martha?

The comment of her “becoming more complicated to manage” as she’s grown older sounds much more reminiscent of dementia than of schizophrenia, as with schizophrenia, symptom severity is often rather clear at a relatively young age (twenties and thirties) and does not necessarily worsen over time.

Summary: All told, the documents I reviewed appear to paint a picture of Martha being described as a patient with dementia. Her case was then apparently to be described to physicians in primary care settings in an attempt to open their minds to prescribing Zyprexa. Martha’s symptoms do not seem related to schizophrenia; rather, they seem to more strongly resemble symptoms of dementia. In addition, an email indicated that at least some Lilly employees thought of Martha as a patient with dementia and that some physicians were upset that they perceived Zyprexa was being marketed for dementia.

For more on the story of Zyprexa’s marketing, please see the following (1, 2, 3, 4)

Disclaimer: Please note that I am not equipped to state whether Lilly’s marketing practices regarding Zyprexa were illegal, as the law seems to be pretty unclear on this point.

Of course, whether a practice is legal and whether it is ethical are two different things.