Metyrapone, a compound that inhibits the body’s production of steroids, seems to accelerate and augment the effects of serotonergic antidepressant drugs, the results of a trial suggest.

Depression is associated with a disturbance of the feedback mechanism - called the HPA axis - that keeps hormones in balance, explain Dr. Holger Jahn, of the University Hospital Hamburg-Eppendorf in Hamburg, Germany, and colleagues in their report.

To test the idea that metyrapone might reduce depression by directly targeting altered HPA-axis activity, the researchers randomly assigned 63 patients hospitalized for major depression to treatment with metyrapone or an inactive placebo for 3 weeks.

In addition, the participants were also treated with the standard antidepressants Serzone or Luvox.

After 21 days, significantly more patients in the metyrapone group exhibited a 30 percent reduction in depression scores, Jahn’s team reports in the Archives of General Psychiatry.

Two weeks after the metyrapone and placebo treatment were ended, those given the active drug still had better response rates, with 19 and 10, respectively, achieving a 50 percent reduction in depression scores.

Analysis also revealed a significantly shorter time to improvement in the metyrapone group.

There were no serious adverse events, although metyrapone was associated with more reports of nausea and headache.

“Although steroid-synthesis inhibitors are not quite ready for routine clinical application,” the investigators write, “the findings of this study clearly warrant further studies aimed at identifying subgroups of depressed patients who will benefit most from this approach.”

SOURCE: Archives of General Psychiatry, December 2004.