Tuesday, April 14, 2009

Abilify Marketing Blitz: Atypical Antipsychotics Gone Wild

"The results are extremely unimpressive; they just squeak by," says Massachusetts psychiatrist Daniel Carlat, editor of the respected Carlat Psychiatry Report. For a clinician or a patient's family, the difference between those on Abilify and those who took a placebo "would be hard to actually see," he adds.

Dr. Carlat is referring to the comparison between Abilify and placebo in the treatment of depression, a topic I have discussed in depth previously (1 , 2 , 3, 4). The above quote comes from a Melissa Healy piece in the Los Angeles Times that throws a damper on Abilify's parade through depression.

Another Melissa Healy piece from the LA Times starts off as follows:
About a year ago, patients began trooping into the office of UCLA psychiatrist Andrew Leuchter, asking whether an antipsychotic drug called Abilify "might be right for them." Few appeared to be delusional, plagued by hallucinations or suffering fearsome mood swings. Mostly, they were depressed or anxious, and frustrated by the pace of their recovery.

Leuchter wondered what was up: Depressed patients didn't usually seek out drugs used to quell psychiatry's most disturbing symptoms.

What was up, he soon discovered, was spending on a new advertising campaign touting Abilify as an "add-on" treatment for depression. For the first time since the arrival of a new generation of antipsychotic medications -- six drugs called the "atypicals" because they work differently from the earlier generation of antipsychotic drugs -- the makers of one, Abilify, had been granted the legal right to market to a vast new population of patients beyond those with schizophrenia or bipolar disorder.
Here's Bristol-Myers Squibb's advertisement for the drug:

This is classic. BMS notes that two-thirds of depressed patients who take antidepressants will still have symptoms after a course of antidepressants. And they have a point: Antidepressants ain't exactly miracle pills. So the commercial implies that Abilify must be really helpful... But if patients add Abilify to their treatment regimen, then only about 25% of them experience remission of depressive symptoms. Isn't it a bit strange that Abilify is appealing to the two-thirds of patients who still have depressive symptoms after taking an antidepressant and offering them a treatment that will lead to remission for only one-quarter of them? Of course, no studies have compared adding Abilify to adding another antidepressant, adding psychotherapy, adding an exercise routine, or adding anything except a placebo. Oh, and given that Abilify led to remission of symptoms in about 25% of patients, while placebo led to remission in about 15% of patients, um, that's a pretty small difference. And keep in mind that the studies were designed in a manner that was almost sure to find a benefit for Abilify, as I have noted previously.

If Abilify was generally benign, then a relatively small benefit over placebo is acceptable.
But, as I mentioned previously, the side effects are troubling. I took issue with a BMS-funded journal article/puff piece that tried to spin side effect data on Abilify:
The authors note that "adjunctive aripiprazole is relatively well-tolerated in patients with MDD." Relatively? Relative to what -- being hit with a baseball bat repeatedly? They note that akathisia occurred in 25% of patients on Abilify compared to 4% of patients on placebo. Restlessness: 12% vs. 2%; insomnia: 8% vs. 3%; fatigue: 8% vs. 4%; blurred vision: 6% vs 1%. The authors report that akathisia resolved in 52% of patients by the end of the study, which would also mean that for 48% of patients with akathisia, they were stuck with it at the end of the study. But don't worry, it's "relatively well-tolerated."
You gotta like any drug that induces akathisia at the same rate that it induces symptom remission. Psychiatrist Doug Bremner had a similar take on Abilify as showing a poor cost-benefit ratio. For a few descriptions of akathisia, see comments at this post on Furious Seasons.

Given the unimpressive scientific data regarding Abilify for depression on one hand and the drug's exploding sales on the other, I was sure glad to see a big paper such as the LA Times note that there really is a controversy here. And if Seroquel receives official FDA approval as an add-on treatment for depression, get ready for the marketing machine to reach a fever pitch. Viva Zyprexa, anyone? Melissa Healy covers the expansion of atypical antipsychotics from schizophrenia and bipolar disorder into depression in an article that y'all simply must read. I'll close with a sad-but-true quote from Yale psychiatry professor Robert Rosenheck:
The story's pretty clear, and pretty embarrassing for the profession of psychiatry, which has allowed itself to be led by marketing," says Robert Rosenheck, a psychiatrist at Yale University who has studied the effectiveness and expanded use of the atypical antipsychotics. "We know now what these companies' strategies are: The number of people with schizophrenia is limited, so the road to profitability goes through soccer moms. They need to market these drugs to ordinary people who have dissatisfactions in life.


Doug Bremner said...

This sorry chapter in psychiatric history (atypicals for depression, in general) may actually have a silver lining in that it serves as a wake up call about what is wrong and why.

Bernard Carroll said...

Don't expect the patients who develop diabetes and tardive dyskinesia unnecessarily to appreciate the silver lining. I recall the flood of lawsuits in the 1970s and 1980s when the first wave of antipsychotic use in nonpsychotic depression occurred. Look for another cohort this time around.

Bernard Carroll.

Bernard Carroll said...

The leader of the pack of compromised KOLs pushing Abilify for depression is Charles Nemeroff. He chaired 2 multi-city road shows promoting Abilify for nonpsychotic depression last year. Nemeroff also is on record with compromised, incompetent, and reckless recommendations on Medscape. See http://hcrenewal.blogspot.com/2008/06/medscapes-cme-ethics-part-ii.html

Other notable KOLs lending their names to this marketing campaign are Michael Thase at Penn, Madukhar Trivedi at UT Southwestern, Craig Nelson at UCSF, and Maurizio Fava at MGH. See http://clinpsyc.blogspot.com/2009/03/abilify-depression-and-memory-hole.html

Julien Benda called this sort of thing la trahison des clercs.

James said...

It is true that much money is spent for health information, but it is also quite true that so far no will find the cure for terrible diseases and quickly became generalized in our body, it calls on the authorities to better distribution of this money because it is spending so far in vain, I have friends who suffer from cancer, HIV, Alzheimer's, and so far we can not find any solution to the disease, only the medicines in vicodin to control their pain, but until you take the same? actually there will be some day, the cure? Please have to be sensible and remember that nobody is free from disease and therefore it is important for everyone.

Anonymous said...

The drug industry’s practice of combining two older company drugs into a single pill is particularly troublesome. Once these combination drugs reach the marketplace--safety for adults aside--some physicians will inevitably prescribe them to children inappropriately. Philip Dawdy commented on the risks of such practices, here: http://www.furiousseasons.com/archives/2009/04/7_year_old_boy_on_prozac_zyprexa_combo_hangs_self.html

In my view the public interest would be better served by allocating public and private resources to basic research for developing less toxic drugs.

I am interested in what readers perceive as the purpose and utility of clinical research on the effectiveness of combinations of drugs within the same class. Here is an example:

laurence said...

Great blog, amazing post, keep up the good work...

ePsychology said...

Unfortunately... bills do not really help. Try psychotherapy. I know what I am talking about.

Unknown said...

I discontinued abilify because of akasthia. Shortly after discontinuing Abilify I experinced extreme dry mouth and frequent urination. A blood test indicated that I had developed diabetes. My doctor was very surprised as he said I am not the typical example, as I am in good shape and regularly participate in triathlons. I am now on insulin therapy and am dissappointed that a drug that's advertised as an effective adjunctive therapy for depression can be so harmful.