Wednesday, June 07, 2006

STAR*D is Bunk

There has been plenty of news over the past year about the long-awaited and much-anticipated STAR*D trial. It was designed to be a study to address real-world approaches to treating depression, in real-world settings.

The major articles are:

Trivedi MH et al. Evaluation of Outcomes with Citalopram for Depression Using Measurement-Based Care in STAR*D: Implications for Clinical Practice. American Journal of Psychiatry. 163:28-40 2006

Rush AJ et al. Bupropion-SR, Sertraline, or Venlafaxine-XR after Failure of SSRIs for Depression. New England Journal of Medicine. 354:1231-1242 2006

Trivedi MH et al. Medication Augmentation after the Failure of SSRIs for Depression. New England Journal of Medicine. 354:1243-1252 2006

Many reviews of the articles are already readily accessible, so I won't describe the articles here.

There are many very interesting pieces of data from these studies. One of the things that I found most interesting was the epidemiological survey of people who tend to get better with citalopram (young, educated, privately-insured women who make a decent amount of money).

Some of my concerns about the articles are:

  • The authors completely botch the use of the term remission. The STAR*D authors think that remission can be determined at a single point in time. They say that scoring below 7 on the HRSD-17 or below 5 on the QIDS reveals remission. This is not true. Remission can only be determined if a patient maintains that low score over time! For all we know, the "remitters" may have become depressed again the day the trial stopped. Remember, also, that remission is not cure. The definitions of "response" and "remission" were co-opted by psychiatry from oncology. If we co-opt the words, we must also maintain their actual meanings.

  • Speaking of the HSRD and the QIDS, take a gander at the "switch" paper, by Rush. The authors are running their trials from two completely different outcome measures! Look at page 1235: remission is based on a HRSD-17 score of less than 7. This is a completely different outcome measure from the primary outcome measure used in the first-step trial (the citalopram -only one): QIDS-C < 5. In a set of trials, why would the authors use different primary outcome measures?

  • It gets worse! In the "augmentation" trial by Trivedi, there are two different primary outcome measures! Come on, guys! Which is it? Look at pages 1244 and 1245. Page 1244 states that the primary outcome is based on the QIDS, whereas page 1245 states that the primary outcome is based on the HSRD. Did the authors base their results and conclusions on whichever scale gave them the best data?

  • Remission rates were somewhere between 28% and 33%. This isn't too great. I know many of you would say "at least we have that." I wouldn't be so sure. Take a look at the augmentation data. The augmenting drugs were bupropion and buspar. Buspar?? As an antidepressant? Buspar hasn't shown efficacy as an antidepressant. In this trial, it is effectively a placebo!. Here's the big point: we do have a placebo arm! Now, compared with placebo, the bupropion-augmentation remission rate was not significantly different: 29.7%-30.1%. Not much different from the citalopram remission rate, huh? Is this all placebo effect?

I should probably stop there. There are many very interesting things about these trials, most of which have not received attention so far (teaser...look at the suicide data). I will write about those later.

What do you think?