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Treatment-Resistant Depression: Figure Clarification

Treatment-Resistant Depression: Figure Clarification

I was disappointed to see the Figure titled "Olanzapine and fluoxetine in the treatment of TRD" in the article "Treatment-Resistant Depression: Strategies for Management" (Psychiatric Times, page 34) in the October 2006 special bonus edition.

The Figure in this article is misleading and out-of-date. It shows strikingly positive results in treatment-resistant depression (TRD) with the combination of olanzapine (Zyprexa) and fluoxetine (Prozac), which were derived from a study in which the total sample size was 28.1
However, in the larger follow-up study by the same research group with a much larger sample (500), the combination of olanzapine and fluoxetine failed to separate from the other therapies at the end point.
2

Edmund S. Higgins, MD
Charleston, SC

Dr Higgins is clinical associate professor of family medicine and psychiatry at the Medical University of South Carolina in Charleston.

Dr Ruelaz responds:
I would like to thank Dr Higgins for reading the article and taking the time to highlight additional information. The differences between the findings of the original and subsequent studies by Shelton (cited above) point out the need for continued large-scale investigations of important preliminary studies like the 2001 Shelton study.

However, the most important finding from the Shelton study that was published in 2005 is that patients randomized to continued nortriptyline (Aventyl, Pamelor) therapy had robust improvement during the 8-week, double-blind treatment phase. What this suggests is that the design was flawed and patients entering this study were not truly treatment-resistant.

In contradistinction, the 2001 Shelton study was a single-site study in which patients were carefully evaluated and met criteria for treatment resistance. I felt that it was important to include the findings from the first study and I then went on to mention studies with other agents that also showed value in adding antipsychotics for TRD. Because of the questions raised by the 2005 Shelton study and the limited space for explaining them, discussion of it was not included in the article.

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