Sowing the Seeds of Lexapro

I'm reading an article with my jaw completely agape and I thought I'd share the pain. The good people at Forest Pharmaceuticals have put together a tragic waste of journal space. The editorial board at the journal Depression and Anxiety should call an emergency meeting to see how this thing got published. Any peer reviewer who put a stamp of approval on this should be forced to listen to Michael Bolton's Greatest Hits at maximum volume for 12 hours straight.

OK, so what am I having a fit about? Here's what happened in this so-called study. 109 primary care doctors were recruited to participate, for which they were doubtlessly paid a decent chunk per patient (not discussed in the manuscript). The lucky depressed patients of these physicians then received escitalopram (Lexapro) for six months. The manuscript mentions that the "investigators" (the primary care docs) "were not required to have previous clinical research experience to be selected for this study." Yeah, no kidding.

There was no control group, and there had already been dozens of studies on the effects of Lexapro in depression, so how are we getting any new info out of this study? Maybe because this is investigating Lexapro in primary care settings; maybe there was no research on that beforehand. Well, no. The manuscript writes that "The efficacy and tolerability of escitalopram in MDD have been extensively evaluated in primary-care settings," citing four relevant studies. So the study is actually not an attempt to answer a scientific question. So what, exactly, is this study?

Looks and smells like a seeding trial, about which Harold Sox and Dummond Rennie wrote:

This practice—a seeding trial—is marketing in the guise of science. The apparent purpose is to test a hypothesis. The true purpose is to get physicians in the habit of prescribing a new drug. Why would a drug company go to the expense and bother of conducting a trial involving hundreds of practitioners— each recruiting a few patients—when a study based at a few large medical centers could accomplish the same scientific purposes much more efficiently? The main point of the seeding trial is not to get high-quality scientific information: It is to change the prescribing habits of large numbers of physicians. A secondary purpose is to transform physicians into advocates for the sponsor’s drug. The company flatters a physician by selecting him because he is “an opinion leader” and incorporates him in the research team with the title of “investigator.” Then, it pays him good money: a consulting fee to advise the company on the drug’s use and another fee for each patient he enrolls. The physician becomes invested in the drug’s future and praises its good features to patients and colleagues. Unwittingly, the physician joins the sponsor’s marketing team. Why do companies pursue this expensive tactic? Because it works.

So these primary care doctors now feel like "researchers," even though their investigation had essentially zero scientific merit. That probably makes these "investigators" feel important -- and the association between feeling important/scientific and Lexapro is a feeling Forest was banking on to increase Lexapro prescriptions in Canada.

Findings: So what did this extremely important piece of seeding, er, research find? Get ready... Lexapro is safe and effective. To quote the authors: "Escitalopram was well tolerated, safe, and efficacious. Escitalopram can be used with confidence to treat patients with MDD in Canadian primary-care settings." And "As adherence to antidepressant treatment is paramount to achieving long-term recovery, the present results suggest that escitalopram should be considered among the first-line choices of antidepressant used in primary care." So with no control group, we can determine that a Lexapro prescription should be among the first things that come to mind when treating depression. This is mind-boggling. This journal often published good work, but this is among the most uninformative pieces of research I have read. Unless one is thinking about marketing, in which case it is very enlightening.


Citation: Pratap Chokka, Mark Legault (2008). Escitalopram in the treatment of major depressive disorder in primary-care settings: an open-label trial Depression and Anxiety, 25 (12) DOI: 10.1002/da.20458

Lexapro is Waaaaaay Better than Celexa (?)

...according to Forest Labs. Dr. Roy Poses at Health Care Renewal received a letter telling him about the dangers of using citalopram versus using Lexapro. As you may recall, Lexapro (escitalopram) is essentially a one-off copycat of Celexa (citalopram). An urgent letter was recently sent out from a marketing firm (which was hired by Forest) to inform doctors that evil managed care firms may attempt to switch their patients from Lexapro to generic citalopram. Now, I'll agree that if someone seems to be doing well on a medication, it would seem odd to change their medication. I don't think there is any firm evidence on what would happen if you switch someone from a drug A to drug B, which is nearly identical to drug A (i.e., escitalopram to citalopram), but one could certainly wonder about the merits of drug switching.

In any case, the letter then goes on to make some astounding claims, including [bold font in original letter]

The clinical profile of Lexapro and citalopram are distinct, as illustrated by the following:

- Lexapro is effective in the treatment of major depressive disorder (MD) and generalized anxiety disorder (GAD). In contrast, citalopram is not indicated for GAD, or for any other anxiety disorder. [citations were to the respective drug labels.]

- There is clinical evidence for the greater efficacy of Lexapro vs. Celexa

...among others. For a very nice analysis of why these claims are misleading, please read the full post at Health Care Renewal. My two cents on why the claims are misleading is as follows:

• Since its patent was running out, Forest opted to not seek FDA approval for any anxiety disorders. No study has ever compared the two compounds in treating anxiety. While true that citalopram is not FDA-indicated, this should not be taken as a sign that it would perform worse than escitalopram in anxiety. Indeed, across the class, SSRIs are efficacious (in the short-term, and not a lot better than placebo) for anxiety.
• The evidence cited to support the greater efficacy of escitalopram over citalopram is very weak. It comes from looking only at the few instances where escitalopram showed a very small advantage over citalopram and ignoring the great majority of the evidence that suggests equivalent efficacy of the two compounds. An excellent article by Svensson and Mansfield laid this issue to rest years ago. Here's what they said regarding Forest's prior advertising claims that Lexapro is more effective than Celexa:

"The advertising claims are not justified because they are based on secondary outcomes, non-intention-to-treat analyses and arbitrarily defined subgroups. The subgroup results are inconsistent. Methodological flaws in the trials could account for the differences found. Even if the differences claimed were real they appear too small to justify higher prices."

My thought is that the letter may have something to do with managed care policies, but it is also a stealth advertisement for Lexapro as being the most efficacious SSRI. After all, if it is "better" than Celexa, then maybe it is "better" than other SSRIs. Of course, this would not be the first time that something Lexapro-related was looking at the scientific evidence through rose colored glasses.