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HEALTH | winter 2002

New Promise of a Fast-acting Drug for Psychotic Depression

Ms. Winter 2002

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Mifepristone—First famous as the early-abortion pill RU486—may turn out to be the best hope yet for severe depression, the kind that leads to paranoia and psychosis. In cases of psychotic major depression—meaning that accompanied by demonic delusions and suicide attempts, not just a few days of “weepy baby blues” or feeling low—it may even be life-saving.

The tragedy of Texas baby-killer Andrea Yates comes to mind.

African-American womanIn the early trials with the drug at Stanford University Medical Center, the promising results were not just for women only. Though women report deep depression more than men do by a two-to-one margin, men are four times more likely to commit suicide. In the Stanford study, both sexes suffering from psychotic major depression responded quickly and positively.

What is particularly exciting about the response to mifepristone (miff-eh-PRI-stone) is that the study participants 19 women and 11 men—suffered from the type of mental illness that improves either slowly or not at all with standard medications and treatments. "Some people in the study who had been sick for years began doing extremely well after just a week," said Alan Schatzberg, chair of the psychiatry department at Stanford.

Typical treatment for psychotic major depression (PMD) is usually a combination of strong antidepressants and antipsychotic medications, but it is effective in only 60 percent of the cases. Electroconvulsive therapy (once called electroshock treatment) works for roughly 80 percent of the patients who try it, but many refuse it because of the stigma associated with it, says Stanford psychiatry professor Charles DeBattista, who worked with the patients in the mifepristone study. "This could shift how we do things in psychiatry in the next few decades," he said. "It may be a way to get very rapid relief to people."


"It's one thing to have political perspective, which all of us do," Senator Hillary Rodham Clinton said recently, "but we are going to be in trouble in this country if we start moving toward theology-based science or ideological research." Though loyally Republican, Nancy Reagan might agree: she is credited with a "whisper campaign" to get rid of the Bush administration's partial limits on stem cell research, which promises help with Alzheimer's, the disease that afflicts President Reagan.

As if to prove Senator Clinton's point, the Bush administration's choice to head an FDA advisory committee on reproductive health is a radically conservative Christian obstetrician/gynecologist who prescribes scriptural readings to treat post parturn depression and, according to Time, PMS. Now a new worry has surfaced: could abortion opponents jeopardize timely FDA approval of important new uses of the abortion drug mifepristone-or even get the drug banned altogether?

While mifepristone is being fast-tracked for approval at the Food and Drug Administration for use in treating psychotic major depression—the first antipsychotic drug given such an expedited review—it remains at the center of a swirl of controversy due to its use as an alternative to a surgical abortion in the first nine weeks of pregnancy. Though mifepristone has been used by more than a million women worldwide, a coalition of conservative women and anti-abortion organizations continues to lobby against its acceptance. Concerned Women for America, together with the American Association of Pro-Life Obstetricians and Gynecologists and the Christian Medical Association, filed a "citizen petition" in August asking that the FDA rescind its 2000 approval of mifepristone as an abortion drug, claiming it is responsible for serious adverse effects, including two deaths. The FDA so far has not responded to the petition directly. However, the company that distributes the drug, Danco Laboratories, sent physicians a letter approved by the FDA—that no cause-and-effect was established between the drug and the deaths. Yet the landscape for mifepristone at the FDA may be changing.

At press time, the Bush administration's controversial choice to head up the FDA's influential 11-member Reproductive Health Drugs Advisory Committee is Dr. W David Hager, a spokesman for the Christian Medical Association, quoted on Concerned Women for America’s Web site as an medical expert against mifepristone.

If appointed, Hager would be in a position to urge that the FDA rescind its approval of mifepristone as an abortion option, in spite of the uproar that would certainly ensue if that occurred. While advisory, the committee has strong influence, as no one seriously doubts that politics and science interact at the FDA. However, the saving grace for the research on mifepristone and depression is that it comes under the aegis of the neuropsychiatric division, not women~s reproductive health. Even so, the fear is that research will be slowed if FDA approval of mifepristone is withdrawn, for whatever reason.

"If they get the drug off the market for medical abortions, researchers will not have access to the drug, " cautioned Jennifer Jackman, director of policy and research for the Feminist Majority. "They can say 'We are not against its use for other reasons’ but their actions, if successful, would slow the research to a halt."

Given the safety record of mifepristone, it seems unlikely that the FDA would withdraw its approval. However, feminists with long memories recall the days when what was then known as “the French pill,” or RU486, was banned by the prior Bush administration, hindering research. President Clinton changed this policy shortly after he took office in 1993, allowing the testing that would eventually provide the grounds for its FDA approval as an abortion drug.

Compassionate Use

Private physicians who wish to give mifepristone to their patients for certain diseases--when other treatments have failed--may acquire it from the Feminist Majority Foundation. Approximately 80 patients have taken advantage of this "compassionate use" program. For more information, call 703-522-2214 and ask about compassionate use of mifepristone.

By 1996, when the Stanford team first tested mifepristone for psychotic depression, it was not hard to obtain for research on depression, says Joseph K. Belanoff, a staff physician at Stanford Hospital and lead author of the study, published in the journal Biological Psychiatry. (At the time, the French company making mifepristone gave it away free to researchers investigating it for other uses, a policy that ended when the drug gained FDA approval for medical abortions. Now it must be purchased from Danco.)

In addition to its potential as a fast-acting antipsychotic medication, mifepristone is showing positive results in treating several other disorders, and is in clinical trials at research centers around the country for bipolar depression; breast and uterine cancers; fibroids; and endometriosis. It has also shown some promise for treating ovarian cancer, Alzheimer's, AIDS, prostate cancer; and Cushing's syndrome, a type of depression that may include psychotic delusion.

Bellanoff said mifepristone appears to work for PMD because it blocks the body’s response to the steroid hormone cortisol, high levels of which are indicated as a cause of the extreme symptoms of psychotic depression. The excess hormone is produced by an overactive group of glands, the hypothalamic-pituitary-adrenal axis, and it is thought that mifepristone may reset this axis to produce lesser amounts of cortisol—just as electroshock is thought to do—since improvements in patients persisted even after they stopped taking the drug.

What is especially encouraging about mifepristone is that, compared to other antidepressants and antipsychotics, it has a low incidence of side effects even in doses large enough to work quickly. Nearly two-thirds of the subjects who received doses of 600 and 1,200 milligrams daily showed dramatic improvement in a week or less. More than 40 percent of the patients saw their symptoms reduced by half or better, based on standard clinical measures. Whether or not the patients continued with their other medications made little difference. (To ensure that none of the women who participate in the studies is pregnant, all are rigorously tested before being given the drug.)

Would mifepristone have helped Andrea Yates—now serving life in prison—before she drowned her five children during a wild hallucination? Could it have saved her children? Belanoff would not hazard a guess, but what we do know is that the antipsychotic drug cocktail she had been taking not only had not helped her depression, it may indeed have pushed her over the edge. Mifepristone just may be the answer for others who come after her.