Friday, April 9, 2010

Able Was I Ere I Saw Abilify

You've all seen them. Screaming, direct-to-consumer advertisements for Abilify for use as an adjunct to antidepressant drugs in treating depression. "Only a third of depression responds to an antidepressant alone! Ask your doctor about Abilify!"

Just before these ads started, I predicted that as most antidepressants were going off patent, so that they would be available as cheaper generics instead of just as expensive brand-name medications, we would start to hear about how ineffective or problematic they were. I was right. Newspaper stories and even journal articles on this subject have become more and more frequent. We hear that antidepressants can increase suicidal ideation (misleading, but I won't cover this in this post), how they are completely ineffective for mild to moderate depression, and even how they don't work at all in true Bipolar patients who are in the depressive phase of their illness (Complete B.S. Also not covered here; I describe the hanky panky employed by the authors of a major journal article that came to this conclusion in my upcoming book).

Meanwhile, use of potentially highly toxic "atypical" antipsychotics like Abilify has skyrocketed. Many patients think Abilify is an antidepressant.

Now another atypical, Seroquel (quetiapine) has received an FDA approval for use as an adjunct to antidepressants. Of note is that its manufacturer, AstraZeneca, also tried to get it approved as a treatment for depression all by itself. Even the FDA, which is often in bed with the pharmaceutical companies, rejected this effort.

So what about that one-third business touted in the Abilify ads? It is a totally misleading figure. Notice ads use the word "depression" and not "major depressive episodes." This is important distinction because there are several types of depression. The two most prominent are dysthymia and major depression.

Dysthymia is a chronic mild form of depression that is usually caused by CCS (crappy childhood syndrome) and/or is reactive to ongoing interpersonal difficulties. It has never responded particularly well to antidepressants, but responds better to psychotherapy.

Major Depression, however, is a true inherited brain disorder. While it is often triggered by external stress, it can also occur spontaneously and can occur in otherwise well-adjusted, relatively happy individuals. It is usually self-limited, meaning it often goes away by itself after 6 to 18 months - only to return some time later.

It is characterized by what we used to refer to as "vegetative symptoms," or "diencephallic" symptoms: difficulty staying asleep, loss of appetite with weight loss, poor energy, loss of pleasure from activities that were previously enjoyed by the individual, poor concentration, and loss of sex drive. It is often also characterized by a complete and all-encompassing sense of utter doom, futility, and loss of joy. The more severe form is called "melancholia" and may also be characterized by feeling the worst when one first wakes up in the morning.

While dysthymia may have some of these symptoms, in major depression the symptoms are pervasive and persistent. This means that they are present almost all day almost every day for two weeks straight at the very minimum. People do not "come out of it" when they are forced to go out and do things, while dysthymic depression tends to lessen considerably when the patient is otherwise occupied or distracted.

Clearly there is overlap in the symptoms of the two types of depression, but the distinction is important. If your sample of patients includes both types - as in the more generic use of the word "depression" in the Abilify adds - then the percentage of people in your sample responding to the drugs will be lower. Many so called "empirical" randomized clinical trials of drugs do a terrible job of distinguishing the two types of depression due to their use of symptom checklists, as discussed in a previous post.

Another issue is that patients who do have major depression and do not respond to one antidepressant often do respond to a second or even a third agent. The one third figure in the ad also applies to patients who have only been tried on one agent.

Last, one can have both dysthymia and major depression. This is called double depression. If the antidepressant is given to this type of patient, the vegetative symptoms often go away, but the patient is still left with his chronic mild depression due to his crummy life. It is totally misleading to say that these patients only had a partial response to antidepressants, but these folk are also included in Abilify's one third figure.

The last point I would like to make is that we have always known than antipsychotics can augment antidepressants in some patients who don't respond to the antidepressants alone - the old ones do this too. However, an antipsychotic augmentation strategy is the last one a good psychiatrist will employ. (I am not referring here to depressed patients who actually become psychotic - hear voices, have delusions, etc.- when they go into a major depressive episode. In these patients, an antipsychotic combined with an antidepressant is the first choice). Lithium and thyroid hormone can also augment anti-depressants, and are far safer. Even one of the managed care panels I am on sent out a newsletter trying to make that point with psychiatrists!


  1. You wrote that many people think that Abilify IS an antidepressant. Well, in fact, it is. Any drug which lowers, say, a Hamilton-D score is an antidepressant. Are you suggesting that some quality other than clinical improvement determines whether a drug is an antidepressant. If so, then there must necessarily be an antidepressant that doesn't work at all. You probably think Prozac is an antidepressant too.

  2. Anonomous,

    Cocaine would lower a Ham-D score too, but we don't speak of it as an antidepressant. Valium would lower a Ham D score as well because it would improve sleep, so I guess that's an anti-depresssant too according to your definition.

    Knocking Prozac? It is true, after all, that highly effective drugs available generically acually make drug company execs MORE depressed.