Furious Seasons

March 24, 2009

Lexapro For Teen Depression Studies: Not Much Efficacy

I heard back from Forest Labs' outside PR person this morning and she provided me with citations for published studies of Lexapro and Celexa in adolescents that were used as the basis for approving Lexapro for major depression in 12 to 17 year olds.

One study appeared in the American Journal of Psychiatry in June 2004 and measured the effectiveness of Celexa not Lexapro. The study found:

"Additionally, at endpoint more citalopram-treated patients (36%) met the prospectively defined criterion for response than did placebo-treated patients (24%), a difference that was statistically significant."

That's not particularly impressive performance and probably barely crosses the threshold of statistical significance. What's more, the Celexa arm of the study involved only 44 adolescents, so this claimed efficacy and response was only achieved by 16 patients. That strikes me as a very small population upon which to hang, in part, a drug's approval.

A positive study of Lexapro in treating adolescent depression remains unpublished in a medical journal (so it's not gone through peer review yet), but was presented last year at the American Psychiatric Association's annual meeting as a poster. You can view the poster here.

Poster presentations are generally slim on details and this one is no exception. In it, the authors reported that the mean score (meaning average) on the Children’s Depression Rating Scale improved by 18.4 points in the placebo group and by 22.4 points in the Lexapro group. The poster contains no details on what percentage of patients in each group responded to placebo or Lexapro, so it's not possible to say what the effect size is for the drug, at least not until the full study goes through peer review and is published.

Here are the two failed studies, failed meaning that the drug did not outperform placebo:

Journal of the American Academy of Child and Adolescent Psychiatry, March 2006

Journal of Clinical Psychopharmacology, June 2006

So we have two failed studies and a positive study of Celexa with a very small effect size plus a poster presentation of Lexapro and that's what the FDA based its approval of Lexapro for teens upon. My guess is that this drug just barely squeaked through the approval gate, but that's one of those things the FDA will never tell the public. It's pretty clear that Lexapro/Celexa for teen depression sure don't have a ton of efficacy.

Posted by Philip Dawdy at March 24, 2009 11:39 AM

del.icio.us Digg it reddit

Comments

Great investigative work to get all the studies involved!

Posted by: Sara at March 24, 2009 12:16 PM

Thanks. Philip! Now we know that given the choice between Lexapro and a glass of water, the water would have the same effect - and, unless it contains residual pharmaceuticals, the water might well be safer.

Posted by: Lilly NC at March 24, 2009 01:03 PM

effect size: if the standard error reported in the poster is equal to [the standard deviation, divided by (the square root of the sample number)], then a standard deviation is roughly 8.2. I looked up mean and std dev really quickly on this CDRS. Another study had Std dev of 7.8, roughly equal to 8. So, a std dev of 8 at basline sounds like a decent numner to work with here.

Effect size: a common effect size is change score divided by std deviation. So, for this study, esc kids had about 22 point change. 22/8 = 2.75.

The average kid in this study changed 2 and a half standard deviations on this depression scale?

That just does not add up.

If the study recruited kids with very high depression scores (possible), then they may have had a lot of regression to the mean operating. can't say without digging into CDRS more to know typical standard deviations. But effect size of 2.75 is almost unheard-of in depression treatment.

Posted by: MedsVsTherapy at March 24, 2009 01:24 PM

As a matter of fact, both studies you mentioned as failed can be interpreted as positive, and one of them probably was interpreted as positive in the Forest's FDA submission. My guess is that the European study (Journal of Clinical Psychopharmacology) was not formally in the FDA submission.

JAACAP abstract notes: "In a post hoc analysis of adolescent (ages 12-17 years) completers, escitalopram significantly improved CDRS-R scores compared with placebo (least squares mean difference = -4.6, p = .047)."

JCP study abstract also had a tentatively positive result in the pertinent sub-group: "For those patients not receiving psychotherapy, there was a higher percentage of Kiddie-SADS-P responders with citalopram (41%) versus placebo (25%) and a significantly higher percentage of MADRS responders and remitters with citalopram (52% and 45%, respectively) versus placebo (22% and 19%, respectively)."

You can also glean some details of the unpublished studies from the Forest database of clinical trials at http://www.forestclinicaltrials.com/CTR/CTRController/CTRCompletedListStudies. Look at studies SCT-MD-15, SCT-MD-32 and SCT-MD-32a.

Posted by: TSC at April 5, 2009 06:55 PM

RE: TSC
The two studies' authors clearly indicate failure in the tests they designed. But for some reason, you are trying to twist the results by highlighting certain incidental data that was touched upon in the study (JAAPAC's post hoc analysis; JCP's analysis of patients not receiving psychotherapy which the study clearly states was less than a third of the initial study group).
You then point readers to unpublished studies from Forest Labs- whom, you fail to mention, manufactures the drug.
Adding to this your basically anonymous screenname, you'll forgive me for having difficulty seeing your post having been written from an neutral point of view.

Posted by: Alan K. at September 7, 2009 06:02 PM