Phase V, Abilify, and Vanishing Akathisia

If you've been reading about Abilify for depression on this site, you've probably noticed that I've been down on Abilify for causing akathisia in a frighteningly high percentage of patients. In two recent trials, akathisia occurred in 25% of Abilify patients compared to 4% of placebo patients. What, exactly, is akathisia? That's still a matter of some debate. Let's turn to a recent Journal of Clinical Psychiatry article on the topic. Entitled "Akathisia: An Updated Review Focusing on Second-Generation Antipsychotics," the paper purports to provide "a review of the literature on the incidence of drug-induced akathisia associated with the use of second-generation antipsychotics (SGAs) and first-generation antipsychotics (FGAs)."

It provides a few different characteristics associated with acute akathisia, including:

• "Intense dysphoria
• Awareness of restlessness
• Complex and semipurposeful motor fidgetiness"

It mentions "...suicidal behavior has been described in patients with akathisia in case reports, both in patients receiving antipsychotic medication and in patients receiving selective serotonin reuptake inhibitors (SSRIs)."A couple of descriptions from another journal:

• Increased tenseness, restlessness, insomnia and a feeling of being very uncomfortable
• On the first day of treatment he reacted with marked anxiety and weepiness, on the second day felt so terrible with such marked panic at night that the medication was cancelled

So we can all agree that akathisia does not sound like fun.

Now back to the Journal of Clinical Psychiatry review article. What did the authors conclude? "The comparative incidence of akathisia among the newer antipsychotic agents remains poorly characterized." And "...SGAs are generally associated with a lower propensity for movement disorders compared with their FGA counterparts, an emerging body of comparative literature shows that second-generation medications are not completely free from inducing akathisia."

The authors go through a long list of second-generation antipsychotic medications. The drug that receives the least attention is aripiprazole (Abilify). The authors conclude that "in studies comparing aripiprazole with placebo, akathisia rates in the aripiprazole arm were similar in some studies, and higher in others. As with other SGAs, akathisia rates with aripiprazole were lower than those of FGAs." So Abilify causes less akathisia than older medications and it's unclear if it causes more akathisia than placebo. But, wait, wasn't akathisia related to much higher rates of akathisia than placebo in treating depression? Fortunately, the authors had a little trick to erase that inconvenient piece of evidence; they only examined trials trials involving people diagnosed with schizophrenia or bipolar disorder. So the depression studies -- POOF -- vanished, along with their damning data.

Why would the authors want to censor negative data about Abilify? Well, one author is an employee of Otsuka America Pharmaceutical, Inc., and another is an employee of Bristol-Myers Squibb, companies that market Abilify. And the other authors: All but one of them have a financial relationship with Bristol-Myers Squibb. The best part:

Editorial support provided by Maria Soushko, Ph.D., Phase Five Communications, Inc., New York, N.Y., with funding provided by Bristol-Myers Squibb.

So a paper that excludes the most inconvenient evidence regarding akathisia on Abilify had major parts of the writing done by... a medical writer hired by Bristol-Myers Squibb. If one goes to Phase Five's website , the first animation that pops up says "Spinning Your Science Into Gold." I'd say that this article was indeed 24 karat gold. I hereby nominate all authors of the study for a much coveted Golden Goblet Award.




Citation Below:

Kane, J., Fleischhacker, W., Hansen, L., Perlis, R., Pikalov, A., & Assunção-Talbott, S. (2009). Akathisia: An Updated Review Focusing on Second-Generation Antipsychotics The Journal of Clinical Psychiatry DOI: 10.4088/JCP.08r04210

Update: See a related post at the Carlat Psychiatry Blog. A partial quote:

Publishing an article that was carefully crafted to draw attention away from Abilify's main liability was shameful, and is exactly the kind of deceptive editorial practice that we as a society can no longer tolerate.

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Friday, May 8, 2009

Abilify Runs Amok, Runs Stealth Safety Campaign in Medical Journal

Furious Seasons has a rather distressing piece of news from a recent Bristol-Myers Squibb conference call. To sum it up quickly, BMS claims that 10.6% of depressed patients are now receiving atypical antipsychotics. Of those 10.6%, 21.7% are taking Abilify. So that would mean roughly 10-11 in 100 depressed patients are taking antipsychotics and 2 of them are on Abilify. I shudder to think how many are on Seroquel. Or Zyprexa. It made me think of a post I wrote a few weeks ago in which I described the marketing of Abilify for depression. A huge market of depressed people just ripe for the picking.

Going along with this, BMS is pushing back on the issue of akathisa, the side effect that has garnered the drug much bad publicity (at least in the blog world; 1, 2, 3) via a medical journal article that distracts attention from Abilify as an akathisia-inducer. More on that to come soon. Ghostwriters, ignoring contradictory evidence; basically, an attempt to completely obscure the evidence on the topic. It's not the first time BMS has successfully placed a study with major flaws into a medical journal (1, 2). Details will be forthcoming.

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Wednesday, April 29, 2009

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

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Thursday, January 8, 2009