Monday, October 17, 2016

Who killed the psychosis challenge study?

Once again this semester I'm teaching an honors seminar on medical research scandals. It's a 24-hour scandal channel: all scandals all the time, two a week for four months, ranging from the historically notorious to the recent and overlooked. Some of the scandals are terrifying because they came and went without much notice at all, such as the exploitative cancer trials that oncologist John Pesando exposed at the Hutch in Seattle, while others, like the Paolo Macchiarini debacle, are fascinating precisely for the opposite reason: they were so lurid and explosive that they blew up an entire institution

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.  


  1. "When the challenge study researchers were forced into the daylight they just shriveled away, like vampires."

    The report of the increase of percentage of the population judged seriously mentally ill, was reported by Whitaker. Whitaker used government numbers of SSI and SSDI Data.
    "the number of people receiving an SSI or SSDI payment because they had been “disabled” by a mental disorder rose from 1.25 million in 1987 to 3.97 million in 2007."

    "In 2014, there were an estimated 9.8 million adults aged 18 or older in the United States with serious mental illness. This number represented 4.2% of all U.S. adults."

    I would like an economist's opinion of the percentage of the working population to confirm the 9.8 million judged S.M.I.
    (that are out of work).

  2. My only question is why those who conducted such Mengelian "studies" were/are not arrested and awaiting prosecution.

  3. One of the Nazi psychiatrists involved in the murder of at least 100,000 mental patients in Germany became president of the World Psychiatric Association many years later. One of the most serious neurological issues among psychiatrists is poor memory. Some psychological problems include lack of conscience, insight, empathy and humility.