Over the past five years, 15 patients at a Maryland research institute agreed to take a chemical that rekindled symptoms of their schizophrenia -- hallucinations, voices, feelings of paranoia.
Scientists studied their symptoms and took sophisticated brain scans that highlighted the biochemical changes that occurred as symptoms flared, then subsided.
In so-called "washout" experiments, scores of other patients agreed to be taken off their medications for weeks at a time so that researchers could study relapse and try new ways to treat schizophrenic symptoms as they appear.
Scientists at the institute, the state-run Maryland Psychiatric Research Center in Catonsville, say the experiments are helping them fulfill an important mission: to learn what causes the devastating mental disorder and -- ultimately -- to find better treatments or even a cure.
But in one of the most contentious debates in medical ethics, critics charge that the studies in Maryland and many other states inflict needless suffering upon people who have trouble weighing the risks and consequences before agreeing to take part. Families, they say, gravitate to research institutes in desperate hope for treatment.
"Families are burdened from trying to save their kids," said Vera Hassner Sharav, director of a New York advocacy group called Citizens for Responsible Care in Psychiatry and Research. "They are trying to get treatment. That's one of the reasons why they are encouraged to go into research.
"That's one reason people become guinea pigs."
The issue is now before the National Bioethics Advisory Commission, which is considering changes in federal rules governing the way scientists recruit patients for psychiatric research. Similarly, an advisory group assembled by the Maryland attorney general's office is considering ways to toughen the state's oversight of psychiatric research.
New rules on the state and federal levels could make it harder for psychiatrists to gain consent before enrolling people in experiments. A regulation under review in Maryland, for instance, would bar the use of many patients in high-risk experiments unless they appoint "surrogates" to make decisions for them.
The Maryland Psychiatric Research Center, part of the University of Maryland, Baltimore, is exclusively devoted to the study of schizophrenia, a mental disorder that causes troubling thought disturbances. People withdraw socially and lose the motivation to succeed. In some cases, they hear strange voices and see things that aren't there.
About 1.5 million Americans are afflicted, making it the most common form of psychotic illness.
The Maryland center is one of many across the country whose experiments have come under scrutiny. In hearings over the past several months, the bioethics commission has heard testimony from parents who said their children were exploited at centers in California and New York as well.
Parents recall suffering
Last September, parents of three patients who enrolled in experiments at the Maryland center in the 1980s and early 1990s charged that their children suffered painful relapses during "washout" experiments. Officials with the research center denying that anyone was hurt, maintain that they have worked hard to ensure that patients volunteering for experiments are mentally competent to do so.
"In 20 years, there hasn't been a documented case of any harm to any of our research participants," said Dr. William Carpenter, director of the Maryland research center. "It's not correct to say that the patients would not be able to speak for themselves. They're not incompetent individuals. They often speak for themselves."
Carpenter said he excludes from consideration any patient who appears too ill to make sound decisions about participating in an experiment. He said patients and their families are fully briefed on the nature and risks of the experiments -- and that the patients are quizzed to make sure they understand what they have heard.
He acknowledged that some experiments are designed to help future patients and may not benefit the participants in any way.
"If there are no potential benefits, that has to be clear," Carpenter said. "We also have to lay out the risks."
The parents' complaints led to a recent investigation by the Office for Protection from Research Risks, a watchdog agency in the U.S. Department of Health and Human Services. In March, inspectors interviewed patients and staff and sifted through several years of research documents.
In a report dated April 15, the office found that the informed-consent documents "generally comply" with federal requirements. But the agency found several "issues of concern" and ordered the center to do a better job disclosing the risks posed by experiments.
Consent forms, for instance, must clearly explain symptoms that might occur when medications are stopped; they must point out experiments that offer "no anticipated benefit to subjects."
Janice Becker, an Annapolis woman who testified before the ethics commission, said her daughter entered a washout experiment in which she was taken off an anti-psychotic drug that had brought her some relief.
"When they took her off the medication that she was on, she was very psychotic," Becker said. "She was obviously in distress, she was panicking, she couldn't sit still. She she sat down, her legs would shake."
Joe Friend, a retired Naval officer from Columbia, enrolled his son as an outpatient in the Catonsville facility in the 1980s. He said his son's condition flared soon after he was taken off his medication in an experiment.
Not long afterward, Friend discovered his son lying in the cul-de-sac in front of the family home. He had taken an overdose of aspirin and was rushed to the hospital, where he was saved.
"Research centers are essential," said Friend, who is a former president of the state chapter of the National Alliance for the Mentally Ill. "But they look upon the patients as subjects. We look upon them as family members."
Such criticism pains Carpenter, who said it represents a minority view and stems from a misunderstanding of what really happened in the studies. Carpenter said he is frustrated that families can publicly criticize the treatment of loved ones, while physicians bound to confidentiality rules are prohibited from fighting back.
But he defends the studies, which he says answer crucial questions about the causes and treatment of schizophrenia.
Patients are sometimes taken off medications so they can later test experimental drugs. Sometimes, scientists perform brain scans to learn what lies at the root of schizophrenia. In some cases, Carpenter said, psychiatrists watch for the first signs of relapse so they can figure out new ways to treat symptoms.
Ketamine experiment
Since 1993, a series of patients have been given a chemical, ketamine, that is related to the street drug, PCP, also known as "angel dust." Scientists have long known that it can induce psychotic symptoms similar to schizophrenia.
Though physicians can recognize the symptoms of schizophrenia, they still don't understand the brain abnormalities that cause them. Dr. Carol A. Tamminga, director of the center's inpatient unit, said the experiment is helping to answer the question.
"We'd like to find out exactly what the mechanism of the illness is so we can turn that mechanism into a treatment." She said the patients are given low doses, and they experience mild symptoms that disappear within about a half-hour.
She acknowledged, however, that the ketamine does not in any way help the patients.
"It's interesting for them to come into the hospital and participate in programs like this," Tamminga said. "The schizophrenic volunteers feel good about making a contribution. It makes their symptoms worse, but they don't become depressed."
Dr. Adil Shamoo, a biomedical ethicist at the University of Maryland School of Medicine, declined to comment on studies done at the research center. But in a general sense, he said experiments that even temporarily make symptoms worse are "appalling."
The ethics debate
"There are literally thousands of patients nationally being used as guinea pigs to test new chemicals, new drugs, and they are putting those patients at very high risk of harming themselves and worsening their prognosis," Shamoo said. "It's unethical, and these types of experiments should stop now."
He said there are more than 200 washout experiments being conducted across the country.
Dr. E. Fuller Torrey, a nationally regarded schizophrenia researcher who lives in Washington, said experiments that induce symptoms should only be done in rare cases.
"There should be a payoff that is imminent enough so that the patient might benefit from it," said Torrey, who nonetheless said the Maryland center is highly regarded. "To say there is no way we can conceive that you're going to personally benefit -- I would have serious questions."
Dr. Steven Sharfstein, president of the Sheppard and Enoch Pratt Hospital in Towson, said patients participating in washout experiments are "pioneers" who are contributing greatly to science. "If they didn't do this, we wouldn't be able to apply new knowledge about the brain and solve a major public health problem," said Sharfstein, who also holds a faculty position at the University of Maryland.
Many psychiatrists and ethicists say the issue is complicated by the conflicting needs to cure schizophrenia and protect confused patients from harm.
"If we were talking about adults of unquestioned competence, we'd say, 'OK, we honor their contribution and are grateful to them," said Dr. Ruth Faden, director of the Johns Hopkins Bioethics Institute. "The problem is, now we've got a class of potential subjects whose competence is at best in question and in some cases judged not to be adequate."
There are only two possible ways to justify high-risk experiments that will not benefit the patients, she said.
"You have to maintain first that the research question was of critical importance," she said. "And second, that there is absolutely no other way to answer the question."
Pub Date: 6/07/98