Sunday, January 11, 2015

Is Abilify Effective for Depression?

Abilify is the top-selling prescription drug in the U.S., a ranking it has held for a couple of years now. What's astonishing is that this drug was originally approved as (and only used as) an antipsychotic. My wife, who has schizoaffective disorder, is an experienced user of Abilify, Haldol, Latuda, Zyprexa, and Saprhis. She will attest to the antipsychotic properties of Abilify (and I'll show a graph for efficacy further below). But treatment of psychosis is not what made Abilify the top-selling drug in the U.S. Abilify is now widely prescribed as an adjunctive drug for depression; plus other uses, both on-label and off-label.

The manufacturer says Abilify is indicated for:
  • Use as an add-on treatment to an antidepressant for adults with Major Depressive Disorder who have had an inadequate response to antidepressant therapy
  • Treatment of manic or mixed episodes associated with Bipolar I Disorder in adults and in pediatric patients 10 to 17 years of age
  • Treatment of schizophrenia in adults and in adolescents 13 to 17 years of age
  • Treatment of irritability associated with Autistic Disorder in pediatric patients 6 to 17 years of age
Physicians and consumers alike have bought into the "Abilify as an adjunct" idea in a big way. Why has this "adjunct" modality become so popular? The main reason is that regular antidepressants simply aren't very effective, and people in a desperate mental state naturally want to know what else can be done other than switching from one ineffective drug to another.

But how good is Abilify, really, as an adjunct to antidepressants? Here is the graph touted on the Abilify website:

Abilify's efficacy (as an adjunct to antidepressants), versus placebo. (Click to enlarge.) The vertical scale plots average change (decrease) in patient scores on the Montgomery–├ůsberg Depression Rating Scale.

This graph pools data from three studies. It shows that the average drop in MADRS score for patients on placebo-plus-antidepressant is a drop of 6.2 points after 6 weeks (from a starting average score of 26). When Abilify is added to the mix, the average score drop is 9.4 points. So if you add Abilify, you can expect a 3.2-point drop in your MADRS score that you wouldn't otherwise have had.

But if you look at the MADRS test, a change in just one answer (e.g., better sleep) could easily produce a 3-point change in your score. What you need to ask yourself is whether this magnitude of change is clinically significant. If you found a dollar bill on the sidewalk, your MADRS score would probably change by 3 points (briefly, of course). If your tax refund was $100 larger than you expected, it would probably mean a 3-point change on MADRS. The point is, the magnitude of change we're talking about here is small. It may be statistically significant, but is it clinically significant?

Abilify's primary use is in treatment of schizophrenia symptoms. Here's the efficacy graph for improvement on the PANSS scale, a common rating system for assessing schizophrenia symptoms:

Abilify efficacy with respect to schizophrenia symptoms (placebo in grey).
This is a much different graph. It shows what anyone would call good separation from placebo: five to eight times bigger change, with Abilify, than with placebo alone.

Abilify costs over a thousand dollars a month (10 mg, 30 pills) if you were to have to pay for it out of pocket. For most patients, this cost is hidden by insurance (or Medicare, in my wife's case). If you were taking Abilify for depression (as an adjunct) and had to pay for it out of pocket, you'd probably find the cost depressing (to the tune of much more than a 3-point drop in MADRS). Still, desperate people will do desperate things. Adding Abilify is "one more thing to try." So by all means try it. But don't expect miracles. If you see any effect at all, it's likely to be a rather small one.

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