Similar to what happened to Robert Spitzer, just as Jeffrey Lieberman released his “untold story of psychiatry” in Shrinks and began his book tour, the very themes he presented as the uncensored truth about psychiatry were being challenged by others. Whose story about psychiatry and its history would the public believe? Although Lieberman did acknowledge in his CBC interview that he was “unfortunately” familiar with Robert Whitaker, he didn’t elaborate on how far back their acquaintance goes.

Like his description of David Rosenhan in Shrinks, Lieberman attempted to discredit what Whitaker and T. M. Luhrmann had to say by his ad hominem assessment of them (see “Psychiatry, Diagnose Thyself! Part 1”). Luhrmann’s work on psychiatry, Of Two Minds, received several awards, including the Victor Turner Prize for Ethnographic Writing and the Boyer Prize for Psychological Anthropology. Anatomy of an Epidemic by Whitaker won the 2010 Investigative Reporters and Editors book award for best investigative journalism. And in 1998, he co-wrote a series on psychiatric research for the Boston Globe that was a finalist for the Pulitzer Prize for Public Service. It was while writing this series of articles that Lieberman and Whitaker first became acquainted with each other.

The first installment of the series, “Testing Takes Human Toll” was published on November 15, 1998. In this article, Whitaker and others described how beginning in 1972, psychiatric researchers used a variety of agents such as methylphenidate (Ritalin, Concerta), ketamine, and tetrahydrocannabinol (THC) “to deliberately provoke psychotic symptoms in more than 1,200 schizophrenic patients.” In some cases, the level of psychosis experienced by these patients was called “severe.” Jeffrey Lieberman was one of those researchers. He conducted methylphenidate challenge tests for more than a decade.

Here is a sampling of three articles where Lieberman was a co-author of studies where methylphenidate was given to schizophrenic patients in order to activate psychotic symptoms.

In a 1987 study, 34 stable outpatients receiving neuroleptic treatment were given an infusion of methylphenidate and then withdrawn from their neuroleptic medication. Three weeks after they were withdrawn from their psych meds, they were given another infusion of methylphenidate. Then the unmedicated patients were followed up for 52 weeks—or until they relapsed; in other words their symptoms returned.

A 1994 study had a similar methodology, 41 stable patients receiving neuroleptic treatment were given an infusion of methylphenidate. They were also withdrawn from their neuroleptic meds and followed for 52 weeks, or until relapse.

In a 1990 study, 38 patients who met the criteria for schizophrenia or schizoaffective disorder were given an infusion of methylphenidate, followed by a regimen of standard acute neuroleptic treatment. This time the patients were individuals who were experiencing their first acute episode of psychosis. The methylphenidate produced an increase in psychopathology reflected by a worsening of their symptoms.

Another 1987 article with Lieberman as a co-author was a meta-analysis of 36 studies that used psychostimulants (PS) in schizophrenia. The authors noted that non-amphetamine drugs like methylphenidate appeared to have a greater “psychotogenic potency.” In other words, they elicited a greater psychotic reaction than amphetamine drugs. “Approximately 40% evidence a psychotogenic response to PS administration in doses that are subpsychotogenic in normal’s.” Don’t miss the fact that Lieberman knowingly used a psychostimulant in his own studies that he knew would elicit a greater, more intense psychotic reaction than amphetamine drugs.

Psychologist Bruce Levine gave a scathing response to Lieberman’s “menace to society” remark concerning Whitaker. He unpacked the pre-1994 studies and questioned the claim that the subject and family members were willing and able to sign informed consent. Levine said: “Who in their right mind would give consent for themselves or for a family member for a procedure that was hypothesized to make a patient worse?”

When Whitaker interviewed Lieberman for the first article in the Boston Globe series, “Testing takes human toll,” Lieberman admitted that the induced symptoms were sometimes “scary and unpleasant.” He even acknowledged that some patients get worse. “But in my experience, the symptoms never exceeded the range of severity that occurred in the course of their illness previously.” Ironically, Lieberman was entirely silent on the topic of schizophrenic challenge studies in Shrinks. They weren’t even discussed as one of the positive examples of how modern psychiatry “now practices an enlightened and effective medicine of mental health.”

Dr. Davis Shore, who was doing ketamine challenge studies for the NIMH, minimized the harm done to patients in challenge studies.  He argued that the increase in symptoms was very short-lived in patients who had experienced them over years. ‘”To say that increasing a particular symptom – like hearing voices for a couple of hours in somebody who has been hearing voices for 10 years – is causing [suffering] rather seems like a stretch.” Here is a 1987 account of one such “stretch” Whitaker saw reported in the scientific literature. The individual was a patient with bipolar disorder who was injected with methylphenidate.

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.

Whitaker’s 1998 series for the Boston Globe is still a worthwhile read. Part 2, written by Deborah Kong, gives more details on “Debatable forms of consent.” She noted how researchers have conceded in court documents that they did not tell mentally ill patients the whole truth for fear of scaring them away from enrolling in the experiments. Part 3 by Robert Whitaker, Lures of riches fuels testing, looks at the influence of the pharmaceutical industry on drug research. In Part 4, “Still no solution in the struggle on safeguards,” Dolores Kong wrote about how the psychiatric community has argued that challenge and washout studies are important avenues to understanding the underlying biology of mental illness. “To this day, some psychiatric specialists are conducting medical experiments in which research subjects are allowed to grow sicker.”

On May 6, 2015, Robert Huber received a letter of apology from the University of Minnesota saying that the university was sorry that his “rights and welfare were compromised.” In July of 2007, Huber was admitted to the University of Minnesota Medical Center with symptoms of schizophrenia, where he was for two weeks. During that time, he was recruited daily to volunteer for a drug trial for an experimental drug called bifeprunox. He was repeatedly told the drug was safe, even though determining safety was one of the goals of the study. In the process of his recruitment for the study, he was also shown “the cost of his hospital care if he didn’t sign up and have the study pick up the tab.”

But there were problems. He experienced severe abdominal pains, which required two ER visits. His records indicated that the doctor in charge of the study thought it unlikely that they were due to the medication. At one point, he contemplated suicide because of the pain. In August of 2007, the FDA decided to not approve bifeprunox, but Huber was not informed of that decision and remained in the study until he withdrew in October of 2007. The university also acknowledged that he was not informed in his consent form of the risks of a medication washout that was necessary before starting the new medication, bifeprunox.

There are several concerns with these kinds of psychiatric research methods. The giving and withholding of medication may create unique risks for the subject. Individuals diagnosed with schizophrenia are at a greater risk of suicide during relapses. Adverse events of all types are more likely to occur as medications are increased or decreased in dosage. George Annas, chair of Health Law Department at Boston University School of Public Health said: “We let researchers do things to people with mental illness that we would never let them do to people with physical illness.”

There are three basic research designs with medications in psychiatry: placebo, washout (where medication is tapered and withdrawn), and challenge (symptoms are provoked in some way). In “Ethics in Psychiatric Research: Study Design Issues,” Gordon DuVal gave a helpful summary of these three research designs. His conclusion was:

Despite a history that has included serious abuses, psychiatric research is important—not least to those who suffer from mental illness. Clinical psychiatric research creates challenging ethical dilemmas. The choice of research design can have significant implications for subject safety and must be carefully considered. While these issues are not necessarily unique to this context, the particular vulnerabilities attending psychiatric illness merit close attention in the design of research involving persons with psychiatric disorders.

DuVal singled out challenge studies as particularly risky, despite the potential research benefits. The risk is that someone who is already sick or vulnerable to a negative response to the challenge “may have harmful symptoms provoked or exacerbated or may suffer a relapse.” He said it was unclear whether the balance of risks and potential benefits can ever justify people in studies where “potentially harmful responses are intentionally induced.” But this is exactly what schizophrenic challenge studies done by Lieberman and others were designed to do. They often have a washout element, which heightens the ethical concerns. “Finally, for practical reasons, challenge studies often require that subjects be deceived, or at best partially informed, about the details of the study.”

A search in Google Scholar found 1,030 entries for “challenge studies”, psychiatry since 2011. This suggests that some psychiatric specialists are still conducting medical experiments in which individuals with various mental illnesses are allowed to grow sicker, and even triggered to so do, in the name of science. This technique is seen as a valuable and necessary element in psychopharmacological research. D. C. D’Souza and J. H. Krystal said in 2001 that: “Psychopharmacological challenge studies have made significant contributions to understanding the neurobiological basis of psychiatric disorders.” They may continue to provide an important method of testing pathophysiologic mechanisms and studying potential pharmacotherapies.

So here’s what I’m thinking. Dr. Jeffery Lieberman writes a book that is supposed to be the untold story of psychiatry for the general public. But he is totally silent in Shrinks about research where psychiatric symptoms are triggered in patients by challenge agents. It’s not given as an example of the scientific standing of the field or the revolutionary process in psychiatry over the past fifty years. His past use of the methods, coupled with his silence, also suggests he still believes that it has a place in psychiatric research. And it certainly is not given as an example of psychiatry’s “long sojourn in the scientific wilderness” in Shrinks along with lobotomies, coma therapy, and fever cures.

Could he have decided to not mention challenge studies, because he thought the public would not accept them or would misunderstand their importance? Worse still, similar to the Rosenhan study, would they be seen as an example of the bankruptcy of psychiatry? Robert Whitaker could connect the dots for the general public between Lieberman and his past challenge studies, so did he become a particular target for marginalization and discrediting by Lieberman? Another possibility is that discussing challenge studies complicates the story of progress and heroism Lieberman wanted to tell in Shrinks. His goal does seem to have been a retelling of the same old rhetoric put forth by the APA since 1980. As Whitaker observed in his review of Shrinks, this mantra was:

The disorders in the DSM are real diseases of the brain; the drugs prescribed for them are quite safe and highly effective; and psychiatric researchers are making great advances in discovering the biology of mental disorders. Therapeutic and research progress are to be found at every turn.

It will be interesting to see what the future holds for psychiatry. Does the given rhetoric of the APA hold sway, or will the growing questions about psychiatry and diagnosis lead to another revolutionary change. Will the public continue to believe Lieberman’s version of the untold story of psychiatry; or will they begin to see it in light of what Whitaker has written? Stay tuned.