Psychiatric Research Ethic
Scientists and Their Subjects Debate Psychiatric Research Ethic
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
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," Brownstein,
39, 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.
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
What is remarkable about the experience Brownstein
describes is that it is so common in psychiatric research. A
large percentage of 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 toxic drugs like ketamine,
an anesthetic related to the hallucinogen "angel dust,"were
given to provoke patients into relapses.
Now, spurred by accounts of their experiences by
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
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
Psychiatric researchers work under special constraints, Hsiao
noted. "We don't have animal models to study, so we have to
do what work we can in humans," he said.
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," 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
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.
Other experiments being examined include a 1994 study in
which 17 patients were taken off their medicines and given
amphetamines to induce psychotic symptoms so the scientists
could view the psychotic states under PET scans, an imaging
technique that is used to assess problems in the brain. In a
1990 study on Long Island, 38 patients who were
experiencing their first psychotic symptoms, but had not yet
been treated, were given a drug called methylphenidate,
which quickly threw 60 percent of the patients into severe
More recently, three studies on children came to light, in
which 100 children from seven 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 injections. No permanent
effects have been observed, but in the experiment, the
children experienced high levels of anxiety, disorientation and
other psychiatric 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," 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
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 that comprehend, 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 of them.
Dr. William Carpenter of the Maryland Psychiatric Research
Center, who has done studies in which patients were taken
off medication, says 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," 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 his
experience as what he describes as 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," Brownstein said.
"They sort of separate themselves from it and watch all this
pain. All for the sake of greater society."
Brownstein has mixed feeling about his experience, and views
current psychiatric research as both "necessary and
"And we need to find a way to make it humane," he said.
Copyright 1998 The New York Times Company
Modified June 26, 2006