They are tormented by demons and at times lost to reality. Now, after years of madness, some schizophrenia patients are being "awakened" by a costly new drug.
By CLAUDIA WALLIS and JAMES WILLWERTH
For weeks they had practiced dance steps, shopped for formals, fretted about hairstyles and what on earth to say to their partners. Now the Big City band was pumping up the volume, and the whole ballroom was beginning to shake. Brandon Fitch, wearing a pinstripe suit and an ear-to-ear grin, shimmied with a high-stepping blond. Daphne Moss, sporting a floral dress and white corsage, delighted her dad by letting him cut in. The usually quiet Kevin Buchberger leaped onto the dance floor and flat-out boogied for the first time in his life, while Kevin Namkoong grabbed an electric guitar and jammed with the band. The prom at Case Western Reserve University had hit full tilt.
But this was a prom that almost never was. Most of the 175 participants were in their 30s; they had missed the proms of their youth -- along with other adolescent rites of passage. Don't ask where they were at 18 or 21. The memories are too bleak, too fragmented to convey. They had organized this better-late-than-never prom to celebrate their remarkable "awakening" to reality after many years of being lost in the darkness of schizophrenia. The revelers were, in a sense, the laughing, dancing embodiments of a new wave of drug therapy that is revolutionizing the way doctors are dealing with this most devilish of mental illnesses.
Daphne Moss, 30, can barely reconstruct her 20s, when she dwelt in a shadowy land of waking nightmares, fiendish voices and the alarming conviction that her parents were actually witches. What she can recall clearly is the moment two years ago when it all came down to one choice: Should she dive headfirst or feetfirst from the third-floor window ledge of her room in a Cleveland boarding house? Feetfirst, she decided. It meant a fractured hip, multiple bruises -- and survival.
Buchberger, 33, also spent a decade wrestling with inner demons. He was hounded by a frightening spirit -- a golden beam of light -- that he believed, had previously haunted an executed murderer. The spirit never spoke. "It tormented me, but I never knew what it wanted," he recalls.
Fitch's memories are just as scary, but in his case the darkness descended at the tender age of eight. Fitch, now 19, spent his early years imagining that historical figures such as Czar Nicholas II lived at his home. He insisted on dressing formally at all times, in a coat and tie or in historical costumes, and he avoided the gaze of people pictured on magazine covers. Watching him boogie the night away at the prom, his mother recalled the last time she had seen her son near a dance floor, six years earlier: "We went to a wedding, and he hid in an alley most of the evening and begged me to take him home."
Moss, Buchberger, Fitch and their fellow promgoers were awakened from their long nightmare of insanity by a remarkable drug called clozapine (brand name: Clozaril). The dinner dance, organized with help from psychiatrists and counselors at Case Western Reserve's affiliated University Hospitals, in Cleveland, served as a bittersweet celebration of shared loss and regained hope. "Those of us who are ill travel on a different road," said prom chairman Fitch in a welcoming address to his fellow refugees from madness. "We would have liked to have gone to our senior proms, but fate didn't give us that chance."
Until quite recently, medicine didn't offer much of a chance either. While doctors and drugmakers have made impressive strides in treating other forms of mental illness, including depression and anxiety, progress against schizophrenia has been painfully slow. Fewer than half of America's 2 million to 3 million schizophrenics respond well enough to the standard treatment with Thorazine (chlorpromazine) and similar drugs to avoid further hospital visits. Most who do respond remain somewhat disabled, and about 80% are stuck with serious and humiliating side effects, including dulled emotions, a clumsy gait known as the "Thorazine shuffle," a compulsive foot-tapping restlessness and an irreversible syndrome called tardive dyskinesia, characterized by twitching and jerky movements of the facial muscles and tongue.
Clozapine is not perfect either. In some patients it causes seizures. A few develop a life-threatening blood defect and must be immediately taken off the medication. It is also extremely expensive, costing $4,160 annually for the drug itself and as much as $9,000 more for doctor-monitored treatment. But for some it brings miracles. Of 20,000 American schizophrenics who did not respond well to Thorazine and were given clozapine, more than half have shown significant improvement: they become less withdrawn, and the nagging inner voices grow hushed. One patient in 10 responds to the drug so dramatically that the effect is like being reborn. "You go from hating the sunshine in the mornings to loving it," says Daphne Moss, who after two years of treatment with clozapine is teaching public school part time and living independently. "In 15 years of practice, I've never seen anything like it," says Dr. Samuel Risch, a psychiatrist at Emory University in Atlanta.
The emergence into sunlight comes gradually. "You don't take something and wake up the next morning," cautions Dr. Herbert Y. Meltzer, director of the Biological Psychology Laboratory at Case Western Reserve's affiliated University Hospitals and one of the leading U.S. authorities on cloz apine. "You see small, steady changes." Still, the 10% of patients who experience a dramatic awakening can be overwhelmed by the bright glare of reality and by the grief of having lost so much time to mental illness. To help patients with this "Rip Van Winkle syndrome," the Case Western group has learned that each small step forward with clozapine must be carefully nurtured with psychological counseling. Without it, the awakened patients can slip back into mental confusion, and the devilish inner voices may begin harping again.
For doctors, patients and anguished families who have coped for years with schizophrenia, the arrival of a new drug that can dramatically help even a portion of the victims is cause for elation. The nation at large should celebrate as well. According to a 1991 study by the National Institute of Mental Health (NIMH), mental illness costs the country $129 billion annually, and schizophrenia alone steals a disproportionate $50 billion -- roughly equivalent to what the Federal Government spent last year on all Medicaid grants. Drugs and doctor bills, hospital beds and police problems add up to $29 billion; lost income and family crises account for the rest.
The cost of schizophrenia can be measured on several scales. By some estimates, fully a quarter of the nation's hospital beds are occupied by schizophrenia patients. Many are chronic abusers of drugs and alcohol, the result of desperate attempts to medicate themselves. The illness can therefore become a one-way ticket to the bottom of the socioeconomic ladder. A third of America's homeless are afflicted, as are about 3% of prison inmates and nearly 6% of those in maximum-security facilities (compared with 1% of the general population). The disease takes a mortal toll as well. About 1 in 4 schizophrenics attempts suicide; 1 in 10 succeeds.
Schizophrenia typically makes its appearance sometime between the ages of 15 and 25, a period when the frontal lobes of the brain are rapidly maturing. Contrary to popular belief, the disorder has nothing to do with "split personality." The term schizophrenia (Greek for split mind) was coined in 1908 by the Swiss psychiatrist Eugen Bleuler and refers to a splitting of the capacity for thought.
The onset is insidious. Victims may begin dressing strangely, sleeping at odd hours, withdrawing from friends and family, whispering to invisible companions or talking back to the television set. They become paralyzed by irrational fears or subject to suspicions that other people are monitoring their thoughts. Eventually the symptoms can no longer be dismissed as the moody vagaries of youth.
Felt from the inside, schizophrenia is terrifying. Here is how one 22-year-old victim described it: "Sometimes people are taking away parts of my body and putting them back. Sometimes I think they are going to kill me." The young man would see huge rats scurrying about his room, and believed others were reading his mind. He heard voices he attributed to "just God and Jesus, but sometimes they sound like my mom and dad."
For families who have watched a child grow and flower, the effect is devastating. "At 15 my son returned to the day of his birth," says a father in Brook Park, Ohio. "He crawled on the floor, and his mother had to diaper him. He withdrew to his room and wouldn't come out except to eat. Once, his voices told him to grab a little girl in a store and undress her. Many times I saw my wife with bruises. I've learned a lot about schizophrenia since she died. I think living with my son killed her."
What causes such bizarre behavior remains mysterious. For centuries schizophrenics were believed to be possessed by devils or even angels. St. Teresa of Avila was probably a schizophrenic, and so perhaps was the prophet Ezekiel, who, in addition to his many apocalyptic visions, said he heard a divine voice command him to sleep on his right side for 390 nights and then switch to his left for 40. Some archaeologists believe that holes drilled in prehistoric skulls represent efforts to release the demons of madness. During the Middle Ages, those who heard voices were frequently burned at the stake. As recently as the 1950s, psychiatrists blamed the disorder on parents, specifically a cold, "schizophrenogenic" mother, though Freud himself had concluded that the illness had biological roots.
Freud, of course, was right. Modern research indicates that the tendency to develop schizophrenia is hereditary. While the average child has a 1% chance of being stricken, the child of a schizophrenic parent faces 10 times those odds, and if both parents are affected, the likelihood jumps to 40%. But genes do not tell the whole story. Children of parents with schizophrenia raised by adoptive parents who don't have the illness have a somewhat reduced risk. In addition, if one identical twin has the disorder, the odds are just 50% that the other will. Clearly, environmental factors -- stress and possibly even a viral infection during infancy or gestation -- also may play a role in triggering the disease.
The first useful treatment for schizophrenia was discovered by accident. A French surgeon serving in Vietnam in the 1950s noticed that Thorazine, then administered as a sedative, quieted ravings and hallucinations among soldiers awaiting surgery. That prompted a Paris psychiatrist to try the drug on schizophrenics. Thorazine calmed patients and reduced their symptoms. It was quickly proclaimed a miracle drug. Thorazine and related drugs such as haloperidol, fluphenazine and thiothixene soon eclipsed the brutal treatments previously in vogue: lobotomy, primitive electroshock and artificially induced insulin shock. Over the next two decades, nearly half a million patients were discharged from state hospitals in the U.S. and hundreds of thousands more from hospitals in Europe.
But the drawbacks soon became apparent. In addition to producing severe side effects, the drugs leave patients listless and indifferent. In short, while they alleviate the so-called positive symptoms of schizophrenia -- the voices and the delusions -- they do not touch the negative symptoms of apathy and social withdrawal. Furthermore, they provide this limited sort of recovery for just 40% of patients; 30% have flare-ups of madness and must be periodically hospitalized, while the remaining 30% are considered to be "treatment resistant" and are largely confined to mental institutions.
Thorazine works primarily by blocking dopamine, one of the many biochemical messengers used by the brain. This discovery, made by Dr. Arvid Carlsson of Sweden in 1967, led doctors to believe schizophrenia is caused by an excess of dopamine. That explanation has now been dismissed by many researchers as too simplistic.
Clozapine was developed by the Swiss pharmaceutical giant Sandoz as an alternative that avoids most of Thorazine's side effects. As a major bonus, it at least partly reduces the passivity of schizophrenics as well as their more blatant symptoms. In contrast to the Thorazine family of drugs, clozapine primarily blocks the neurotransmitter serotonin, though it also inhibits dopamine transmission to some degree. The fact that it influences both neurotransmitters may help explain its greater effectiveness. Still, "nobody completely understands why clozapine is a superior drug," says Dr. Luis Ramirez, chief of psychiatry at Cleveland's VA hospitals.
For all its superiority, the drug almost didn't make it to the U.S. market. Approved in several European countries in 1969, it was quickly withdrawn six years later, after Finnish doctors reported that eight patients taking the drug had died of agranulocytosis, a sudden loss of infection-fighting white blood cells. In the U.S., the Food and Drug Administration halted even preliminary tests. "We assumed it was a dead product," recalls psychopharmacologist Gilbert Honigfeld, who helped develop the drug for Sandoz and is now in charge of marketing it in the U.S. American and European research eventually showed that agranulocytosis occurred in 1% to 2% of clozapine patients and that it could be detected and nipped in the bud by conducting blood tests on a weekly basis.
In 1989 the FDA approved clozapine for patients who failed to benefit from Thorazine-type drugs, but required the weekly blood testing. Then Sandoz, with the agency's approval, added an unprecedented stipulation: only its representatives could administer the blood tests. Technicians representing Sandoz were prepared to travel hundreds of miles to draw a single patient's blood if necessary. The policy boosted the drug's price tag to an astonishing $8,944 a year and raised a fire storm of protest from families, mental-health advocates and state mental-health-department officials, who argued that local technicians could perform the blood tests at a much lower cost. Finally, the controversy was resolved when Sandoz agreed last summer to sell clozapine without company blood testing.
Now at $4,160 a year, clozapine still looms beyond the reach of most who need it. The stiff price has discouraged many state institutions and agencies, which are responsible for the care of the vast majority of American schizophrenia patients. While a few states have embraced the drug -- Minnesota, for example, has provided clozapine to 1,000 of its 4,300 eligible patients -- most have not made that commitment. California, for instance, with 60,000 potentially eligible patients, has treated only 1,300. Veterans hospitals, which treat as many as 9,000 eligible schizophrenia patients annually, have given clozapine to only 300.
In addition, many private insurance companies resist paying for the drug. "The miracle of clozapine has turned into a mirage," says Laurie Flynn, executive director of the National Alliance for the Mentally Ill. "You can see it. You can read about it. But you can't get it." The Flynn family, in Alexandria, Va., had to pay an extra $6,000 in insurance to obtain coverage that allowed their daughter Shannon, 24, to use clozapine. Once seriously ill, the young woman has recovered sufficiently to graduate from Georgetown University and hold a part-time job at NIMH.
Cases like Shannon's indicate that clozapine is a good investment. In fact, a soon-to-be published study by Case Western Reserve's Meltzer concludes that cloz apine can save more than $30,000 a year in medical costs per patient, compared with Thorazine-type drug treatment, by greatly reducing the need for hospitalization and other intervention.
For patients who get the drug, the greatest drawback is the risk of developing agranulocytosis. So far, six of the 20,000 Americans who have been treated with clozapine have died from the condition. Although that is considered a low fatality rate, it is still enough to make mental-health professionals nervous. They worry that the uncertainty and risks might jump in 1994, when Sandoz loses its exclusive license to manufacture clozapine. The appearance of generic versions of the drug may be a boon for cash-strapped families, but it raises the specter of fewer controls -- and more deaths.
The appearance of agranulocytosis -- marked by a drop in white blood cells -- is always tragic. Some patients, when informed that they must immediately go off clozapine, beg to remain on it rather than descend again into madness. Phil, 36, was awakened by clozapine after 13 years of suffering. Thanks to the drug, he was able to work part time in a grocery store and start up a social life. Then agranulocytosis struck, and he had to be taken off the drug. "He has his voices and moods again," his father reports sadly. "We'll just have to wait for something else to come along."
Researchers are working furiously to develop that something else. Janssen Pharmaceutica, a Belgium-based subsidiary of Johnson & Johnson, is in the lead with risperidone, a drug that so far appears to be safer than clozapine and works in the same way. Testing is incomplete, however, and the drug is at least 18 months away from the market. Abbott Labs, Eli Lilly and others are also developing successors to clozapine.
Research into brain chemistry is progressing so quickly that doctors in the frustrating field of schizophrenia finally have reason to be optimistic. "We can do for schizophrenia what we've done for so many major illnesses," insists Dr. Samuel Keith, head of NIMH's National Schizophrenic Plan. "We can dissect and demystify it. Then we can defeat it."
Copyright (c) TIME Magazine, 1995 TIME Inc. Magazine Company; (c) 1995 Compact Publishing, Inc.