And then there are the psychosis "challenge studies," otherwise known as "symptom provocation" studies. You might remember these. Take a patient with schizophrenia, give him ketamine or maybe amphetamine, and watch as he descends into full-blown psychosis. There's no possible benefit for patients, only the chance of harm; the purpose is to study the pathophysiology of psychosis. Here's how one patient reacted, as described in a published article quoted by Robert Whitaker and Dolores Kong in the Boston Globe.
''Within a few minutes after the infusion, Mr. A experienced nausea and motor agitation. Soon thereafter he began thrashing about uncontrollably and appeared to be very angry, displaying facial grimacing, grunting and shouting ... 15 minutes after the infusion, he shouted, 'It's coming at me again, like getting out of control. It's stronger than I am.' He slammed his fists into the bed and table and implored us not to touch him, warning that he might become assaultive. Gradually over the next half hour, Mr. A calmed down and began to talk about his experience.''
Another patient interviewed by Whitaker and Kong, Shalmah Prince, became so psychotic in a challenge study that she was placed in leather restraints. Her psychosis did not abate for ten days. "I was never the same person again,'' she said. ''My perception of myself and who I was completely changed. I had a sense of shame and embarrassment. Who would have ever thought that doctors would create psychosis like that?''
From the early 1970s through the 1990s, psychosis challenge studies were ubiquitous. These studies were not a secret; they were conducted at elite research centers and published in major journals. As Whitaker and Kong write:
This year, according to research protocols obtained by the Globe, Yale University physicians have been recruiting people with schizophrenia for experiments in which they will hospitalize them, stop their medications, and infuse them with tetrahydrocannabinol, the psychoactive ingredient in marijuana. Columbia University researchers have been giving amphetamine to schizophrenic patients so they can take images of their brains while they are psychotic. At the National Institute of Mental Health, in Bethesda, Md., researchers have been injecting ketamine, the chemical cousin of the notorious street drug angel dust, into unmedicated schizophrenic patients.
Looking back at the debate over challenge studies, the first thing that jumps out is how little criticism they attracted, even from bioethicists. If you look at the published articles about the ethics of challenge studies in the medical literature in the late 90s and early 2000s, you'll mainly see articles defending the studies (presumably from outside agitators like Vera Sharav and Adil Shamoo.) A national bioethics commission that looked at the issue issued a tepid recommendation for more examination and debate. In the Globe article, psychiatrist and bioethicist Paul Appelbaum is quoted as saying, ''The investigators [using ketamine] are quite persuasive, from my discussions, that they are not causing outrageous levels of harm.''
The second striking thing is how quickly the psychosis challenge studies vanished. Within several years of the 1998 Globe investigation by Whitaker and Kong, psychosis challenge studies had all but disappeared. If there had been a major scandal involved -- a death, a high-profile lawsuit, a research shutdown by OHRP -- this might not be so surprising. But no such incident occurred. All it took was sunshine. When the challenge study researchers were forced into the daylight they just shriveled away, like vampires.
It's tempting to say that Whitaker and Kong killed the psychosis challenge study. Yet the researchers involved were not sanctioned, or even strongly criticized. One of them -- Jeffrey Lieberman -- went on to become president of the American Psychiatric Association. In this sense, at least, the psychosis challenge study fits into a larger pattern of medical research abuses. Only after the ethical controversy is far in the past is it safe for academic medicine to admit to wrongs and injustice. With psychosis challenge studies, apparently, we have not yet reached that point.