In her most psychotic state, Cheryl heard threatening voices. Faces seen in the trees seemed to laugh at her. While driving one night, she thought a man stepped out in front of her car and she swerved, crashing into a post. This all started in 1989, when after Cheryl's son was born she slipped into a post-partum depression.
"My mind raced with intruding thoughts about killing myself," said the West Coast businesswoman, who did not want her last name used. "I rushed to the kitchen to draw knives, and would catch myself."
Over 13 years Cheryl was hospitalized and treated with antidepressants and hormones, but nothing worked until she entered a clinical trial for a controversial drug that helped lift her out of the darkness: the abortion drug RU-486.
Now, at 53, she illicitly buys the drug from distributors in Asia, traveling two times a year to stockpile 3,000 tablets at a time, at a cost of approximately $10,000.
RU-486 has had a charged history because of the abortion debate. Many doctors are skeptical of the clinical trials on the drug, and worry about unproven benefits and potential side effects, including abortion.
The drug, a synthetic steroid compound known as mifepristone, is known as RU-486 in Europe, and marketed as Mifeprex in the United States. In combination with misoprostol, the drug was used in 161,000 medical abortions in the United States last year, according to the Guttmacher Institute.
When used under doctor supervision, the drug has a strong safety record. Common side effects are vaginal bleeding and cramping, nausea and vomiting, as well as a small incidence of pelvic inflammatory disease, which may be less likely in men or non-pregnant women.
In a highly publicized incident in 2004, the FDA issued a warning about the risk of infection after a California woman died after taking the drug to terminate a pregnancy.
But in clinical trials over the last decade, researchers have been using the drug to treat psychotic depression, a terrifying form of depression that carries a high suicide risk, and for which there are few sure-fire cures.
They say the drug acts on the brain's receptors for cortisol, the so-called "stress hormone."
Andrea Yates, the mother who drowned her five children in Texas in 2001, likely suffered from psychotic depression, believing that she was a bad mother and that her children were "doomed to burn in the fires of hell."
Published studies on RU-486, two of them run by Corcept Therapeutics, the drug's manufacturer, have shown weak short-term effects. But some doctors say this drug, or other cortisol-related interventions, and even related theories on inflammation and depression, may eventually show promise.
The Food and Drug Administration will review an application for use as a treatment for psychotic depression at the end of the year.
RU-486 Treatment for Depression is Controversial
"When people are stressed, we know that there is an increase in inflammation and cortisol," said Kenneth Robbins, medical director of psychiatry at Stoughton Hospital and professor of psychiatry at the University of Wisconsin. "I think this hypothesis is really interesting, and has to do with inflammation and cortisol metabolism, and treating inflammation somehow improves mood."
Other studies have shown an association between depression and inflammation in the area of the brain that controls mood, he said.
"One has to be cautious, though, because depression waxes and wanes on its own, and it's always hard when looking at a small number of people, whether it is the effect of the drug, or if it would go away anyway," said Robbins. "We have to make sure we are careful with the studies. There is a long history of people making claims about substances helping depression."
But, he warns, taking a drug for an off-label use can be dangerous -- and not only for Cheryl's health.
"I have delayed telling my story for so many years, and the main reason is because I am risking my ability to get this drug for my own well-being," she said. "It's a federal offense. RU-486 is a schedule 1 drug, the most controlled we have."
Cheryl, who is uninsurable except in an expensive high-risk pool, said she averages about $15,000 to $20,000 a year on her drugs. Her lucrative high-tech job allows her to medicate herself.
"I am absolutely clear it saves my life and my ability to think, and to be productive," said Cheryl. "I have to make a living as a business consultant and work for my clients and function, and this is the only way I am able to do that. Without it, I wouldn't be here."
In major depression with psychotic features, a person experiences depression along with a detachment from reality, as well as delusions and hallucinations, according to the National Institutes of Health.
A family history of the illness increases risk. Cheryl learned later that both her mother and grandmother had suffered from the same problem illness.
Some hear voices telling them they are evil or they don't deserve to live; others may think their body is filled with cancer and "rotting inside," according to NIH. The risk for suicide is five times that of other forms of depression.
Depression affects about six to seven percent of the population at any given time, according to Robbins. About one to two percent have psychotic symptoms.
"It's a very scary illness," said Robbins.
"Clearly there is some genetic loading," he said. "But in the early course of depression, the first, second or third episode has a precipitant - a physiological or psychological stressor. After you've failed an exam or you think you are going to lose your job - life's stressors are triggers. And it's very common after having a baby."
"Usually the psychotic symptoms thematically associated with depression are very negative. Delusional guilt that things are their fault," said Robbins. "Delusions can also be very scary on the person affected. They hold a false belief, and to reason with them is not helpful."
Doctors treat psychotic depression with antidepressants and antipsychotic drugs, which help to treat the mood and the psychosis. Talk and behavioral therapy are ineffective.
"As is the problem with many mental illnesses, we don't know what the trigger is for depression," he said. "We know there are changes in neurotransmitters, and the treatment is altering them, but we have not had as much success as we would like."
As a last resort, patients may undergo electroconvulsive therapy (ECT).
About 80 to 90 percent get better with ECT, a procedure that is now much "slicker," according to Robbins.
"There is an anesthesiologist who puts you to sleep, and your muscles are paralyzed so you are not flailing around like in a real seizure," he said. "It's not like going back to watching, 'One Flew Over the Cuckoo's Nest,' and you're awake and it's a horrible experience."
"It's not my first choice, but if someone is dangerous enough and we are afraid of his safety, it's the quickest and most successful treatment we have."
Abortion Drug Distributor Has Secret Location
As for the potential for RU-486, which is so highly regulated that the distributor -- Danco Laboratories -- has offices in a secret location so they are not hounded by anti-abortion protesters, Robbins said, "I think we have to keep an open mind."
What interests Robbins is how steroids, which are used to decrease an inflammatory reaction, play a role in depression. And RU-486 is known to decrease the body's steroid system.
"If someone is taking therapeutic doses of steroids for inflammatory problems, like Lupus or any number of things, even poison ivy and asthma, we know that we increase their risk for psychosis and depression," he said. "It's clear that there are significant emotional reactions."
Robbins suspects there may be a correlation between inflammation and depression.
"I personally don't know the answer if [RU-486] works, but I think the theory is worth exploring," he said. "I think it's still premature with this particular drug, but a compelling theory. With the question of inflammation, cortisol and depression, they may be on to something."
Mifepristone was first used to treat psychotic depression in the 1980s in Holland. A doctor in Rotterdam treated a man who thought he was the victim of voodoo rituals, and was nearly catatonic. They discovered the man had cancer of the adrenal gland, which was over-producing the so-called "stress hormone" cortisol.
They gave him RU-486, and in 24 hours, the patient had a dramatic recovery with seemingly no side effects.
Cheryl had a similar reaction to the drug. Her psychosis grew "out of control" over 13 years after the birth of her son.
Looking back, she said the classic triggers for her depression were obvious: a 38-hour labor with a new baby who was colicky, a divorce where her husband joined a cult, and tax problems with her business.
Nine months after her son's birth, she broke down in the doctor's office and was immediately hospitalized for severe depression. "I was a new mother and I wanted to focus on the baby and I was also so ashamed of having those thoughts. I had everything to live for and I didn't understand why I wanted to kill myself," she said.
The doctor recommended a clinical trial after medications failed. In 2002, Cheryl signed up for Phase 2 clinical trials at Stanford University.
"I had a really dramatic reaction," Cheryl said. "After four days, I woke up and had this remarkable feeling, like I had the most restful night sleep, and I couldn't remember sleeping that well in years."
But after the trial ended, the urge to kill herself returned, and Cheryl had that frightening car accident when she swerved with no one was in the road.
She was then allowed two more treatments in trials, and each time her psychoses disappeared. Cheryl searched for a legal way to find RU-486 through a "compassionate use" program, but was turned away.
That's when she decided to seek out the drug on her own. Cheryl travels abroad to bring back the medication that she believes has made life worth living, despite the legal or medical risks.
"I could be dead or I could have some side effects," she said. "Anything else is minor."