RU-486 May Dramatically Relieve Psychotic Depression

RU-486 May Dramatically Relieve Psychotic Depression

from Stanford Medicine Winter/Spring 2001

A preliminary trial suggests that the controversial drug RU-486, a recently approved abortifacient and emergency contraceptive, may provide sudden relief for psychotic depression -- a disease normally very difficult to treat.

"Some psychotically depressed patients are dramatically better within a few days," says Alan Schatzberg, MD, chair of psychiatry and behavioral sciences [at Stanford]. They stop hearing voices and having pessimistic kinds of delusions, like they're dying or the world is ending. We've seen the response within a four day study. This is fairly dramatic."

Traditionally, patients with psychotic depression receive one of two treatments: combined antidepressant and antipsychotic medication, or electroconvulsive therapy (ECT). Even when effective, both treatments are relatively slow and can leave symptoms that last for months.

"With mifepristone (RU-486) there's a very quick intervention. The patients often feel better and then we can put them on conventional antidepressants without the antipsychotics or ECT," Schatzberg says. "What's interesting is that the results are not effervescent. The patients feel better and it lasts. Nobody's had to come back, nobody's had to undergo ECT."

The social implications of the treatment are profound, Schatzberg says, both because mifepristone might eliminate the need for shock treatments and because it comes from a drug with other uses that some people don't like.

Originally mifepristone was developed as a steroid treatment for Cushing's disease, to block the adrenal hormone cortisol. But since progesterone receptors and cortisol receptors are structurally related, mifepristone also blocks progesterone, an effect that makes it useful as an abortifacient and, in smaller doses, as an emergency contraceptive.

Research over the last 17 years has revealed that cortisol, a hormone released during times of significant stress, is extremely elevated in psychotically depressed patients. It seems their sustained levels of cortisol create a chronic stress reaction. This in turn may cause psychotic depression, including memory problems, sleep disturbances and hallucinations.

In a preliminary trial, five psychotically depressed patients were treated with mifepristone and four showed marked improvement within about four days. Further studies are now under way and in need of volunteers. Volunteers who feel that they may qualify as depressed individuals and are interested in participating should contact the Stanford Depression Research Clinic at (650) 725-4620 for an initial over-the-phone assessment.

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