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.

Tuesday, April 14, 2009