The New York Times
May 19, 1998
Psychiatric Researchers Under Fire
By PHILIP J. HILTS
ANDREW BROWNSTEIN, a severe manic-depressive, was desperate. None of his medicines could keep the anxiety and depression of his illness at bay. So in the fall of 1994, he agreed to become a research subject at the National Institute of Mental Health in Bethesda, Md. It would put him, he recalls hoping, at “the cutting edge of medicine,” where he would learn much about his disorder and get superior treatment.
Instead, he said, he was taken off his medicines, subjected to painful tests and given a wide variety of chemical substances to test his reactions. Over the next year, he said, consent forms and explanations of experiments to be done on him were passed out casually, with little attempt to see that he understood. But then, he added, he was very ill and often could not follow what was said to him anyway.
“There were times when I was truly railroaded,” Mr. Brownstein, a 39-year-old resident of South Philadelphia, said in an interview. It was only after months in residence at the institute’s experimental ward “that I slowly realized that my participation would not benefit me directly,” he said.
Mr. Brownstein said he became so distraught that he begged for the doctors to give him shock therapy. He told of buying a hose with the intention of connecting it to an auto tailpipe to commit suicide. When that did not work out, he said, he bought bottles of over-the-counter pain relievers, planning to kill himself with an overdose. But he never carried out the plan.
What is remarkable about the experience Mr. Brownstein describes is that it is so common in psychiatric research. Many drug trials seeking to put new psychiatric medicines on the market use dummy pills and take patients off their medicines.
Federal ethics officials estimate that there have been 100 to 300 experiments in which patients were taken off their medicines when no new medicine was being tried; rather, they were taken off their medicines to observe the patients as they relapsed in order to study the illnesses. Among those experiments were some in which potentially toxic drugs like PCP, a hallucinogen known as “angel dust,” and ketamine, an anesthetic related it, were given to provoke patients into relapses.
Now, spurred by accounts of their experiences by Mr. Brownstein and thousands of other vulnerable research subjects, Federal and state agencies are considering major changes in the rules governing psychiatric research on mental patients and others who might have trouble giving valid consent.
The National Bioethics Advisory Commission, appointed by President Clinton, today begins considering proposals that would require researchers first to test potential research subjects to see if they are capable of giving consent. In addition, they would have to justify high-risk experiments to the local review boards that approve research, and they would have to name legal and medical monitors to whom the patients could appeal during experiments. The review boards, the proposals say, would have to have a patient advocate as well as someone familiar with psychiatric research.
Several states, including New York and Maryland, are also rewriting their guidelines for psychiatric experiments, as are other Federal agencies, including the National Institute of Mental Health and the Office of Protection from Research Risks, which is the watchdog office that investigates violations of Federal law in human experiments.
Psychiatric researchers argue that their studies are important to the understanding and future treatment of mental disorders, and that patients can be deprived of medication for brief periods with little harm.
Speaking for the mental health institute, Dr. John K. Hsiao, a psychiatrist at the institute who is editor of its Schizophrenia Bulletin, said: “We shouldn’t ever do anything that has a significant chance of permanent harm for the patients. But I think we can ask patients to put up with an exacerbation of symptoms. They should be given a chance to contribute to science.”
Psychiatric researchers work under special constraints, Dr. Hsiao noted. “We don’t have animal models to study, so we have to do what work we can in humans,” he said.
Dr. Hsiao did acknowledge, however, that patients sometimes might not understand what they are getting into, because the consent forms and explanations can be legalistic and badly written, and doctors do not always make things clear to research subjects. “We can do better,” he said.
Alexander Capron, an ethicist at the University of Southern California and a member of the Bioethics Advisory Commission, gave a harsher assessment. “Some of these consent forms contain outright deception,” Mr. Capron said in an interview. “They lead patients to believe they are going to get treatment when they are actually going to be taken off treatment and observed while they have horrible relapses of their illness.”
Critics say there is no justification for the high-risk studies.
“Many of these are experiments that give no medical benefit to the subjects, and involve subjects who never should have been asked to sign a consent form,” said Dr. Adil Shamoo, a biomedical ethicist at the University of Maryland at Baltimore who has studied experimentation in vulnerable subjects for years. “There have been several attempted and successful suicides among the subjects of the experiments. There are no other kinds of medical experiments in which you induce the disease in humans to study it.”
One experiment of this controversial type, being examined in the current ethics reviews, was reported last fall in The Journal of Neuropsychopharmacology. Thirteen men and women with schizophrenia were not only taken off their medicines, but then injected with ketamine to provoke psychotic symptoms in the subjects – hallucinations, disorientation, paranoia – so the symptoms could be studied.
Another experiment being examined is a 1990 study on Long Island in which 38 patients were given a drug called methylphenidate, which quickly threw 60 percent of them into severe psychotic episodes.
More recently, three studies on children came to light, in which 100 children from 7 to 10 years old, mostly black and Hispanic, were brought into clinics and injected with the now-banned diet drug fenfluramine. The object was to provoke the production of a brain chemical that scientists believe is linked to aggression and violence.
One study focused on the younger brothers of boys convicted of crimes. The researchers assumed that the younger brothers, raised in “adverse rearing” environments, would also have tendencies to aggression, which might be measured chemically. In the two other studies, the children had been found to have attention deficit and hyperactivity disorder. They were taken off their medications for several weeks while receiving fenfluramine. No permanent effects have been observed, but in the experiment, the children experienced high levels of anxiety, disorientation and other symptoms.
Psychiatric researchers said the studies had valid purposes. For example, the fenfluramine experiments on minority children may provide information on the biological basis of aggressive behavior, said Dr. John Oldham, director of the New York State Psychiatric Research Institute at Columbia University, where the experiments were done.
Aggressive children “are overrepresented in the criminal justice system, and we don’t have a lot of treatment methods for them,” Dr. Oldham said. “If we could learn how to intervene, it could be enormously valuable.”
But Vera Sharav, director of Citizens for Responsible Care in Psychiatry and Research, a New York advocacy group, who has brought many of the studies to light, said psychiatric research was out of control. “For N.I.M.H. to endorse, fund, and even conduct such experiments demonstrates a breakdown in public health policy,” Ms. Sharav said.
Current Federal rules governing human research subjects do not have any special protections or competency requirements for mental patients, who can be used as subjects if they give their consent.
To obtain consent, researchers are required to explain that the experiments are not treatment, but rather research that will not help the patient. The researchers must explain in detail the risks the subjects will face, “in language understandable to the subject or the representative.”
Researchers say the subjects do freely give their consent, but studies of patients’ understanding of what they are about to undergo suggest that fewer than half do so, said Dr. Paul Applebaum, a psychiatrist at the University of Massachusetts at Worcester. It takes special educational sessions with the subjects before they can effectively grasp the meaning of what is being asked.
Dr. William Carpenter of the Maryland Psychiatric Research Center, who has done studies in which patients were taken off medication, said he believes experiments in which patients are taken off their medicines should go forward and are not very harmful to subjects. He said: “If they hear voices 15 times, instead they might hear them 20 times a day. If they get symptoms, that’s not good. That is bad, but it may not necessarily cause them distress.”
But other researchers say the studies entail too much risk to the subjects. Dr. Marvin Herz, a professor of psychiatry at the University of Rochester who is chairman of the American Psychiatric Association committee that wrote the guidelines on treatment of schizophrenia, said experiments like the one with ketamine simply should not be done.
“If you take a person off his drug treatment, there has to be a very good reason for that, such as a very promising therapy to test, and even then, it’s a difficult choice,” Dr. Herz said. “I believe once patients relapse, some never get back to their previous baseline, to their previous level of living.”
As for Andrew Brownstein, only now, three years after leaving the ward, is he beginning to recover from what he describes as being a “guinea pig.”
“I don’t know how doctors can watch you be in that kind of pain, and not do anything to help you,” Mr. Brownstein said. “They sort of separate themselves from it and watch all this pain. All for the sake of greater society.”
Dr. David Shore, director of research at the mental health institute, said: “This institute takes human-subjects research very seriously. We are looking into allegations by some patients, but because of confidentiality requirements, we cannot talk about what may or may not be true in a particular patient’s medical record.”
Dr. Shore said the institute would soon release a report on patients who are taken off their medications. That report, he said, would deal with the issue of balancing the needs of science and the suffering of patients in experiments.
Indeed, Mr. Brownstein has mixed feelings about his experience, and views current psychiatric research as both “necessary and inhumane.”
“And we need to find a way to make it humane,” he said. (Pge F-1; Column 2; Science Desk)