What you might write in a blog post or argue in a comment may be very different from what needs to be done in the very next case you see. Say you are strongly drawn to the point that antipsychotic medicine is toxic and should rarely be used. Further you may be sympathetic to Thomas Szasz’s view that mental illness is a myth and personally opposed to involuntary hospitalization. But then you meet someone like Dan Markingson whose mind is filled with compelling paranoid ideas and who is driven towards violence. It’s the kind of case where acting on your ideology would be in error. Dan’s involuntary hospitalization and medication with an antipsychotic was the only rational choice. Likewise, there’s no algorithm that dictates which medication, or how much, or the duration of his confinement. These are all things contingent on his response, not preconceived ideas based on ideology or guideline.
What happened several days later defies understanding. In Minnesota, committed patients can be offered another option, a stay of commitment, and avoid being confined to a mental institution as long as they agree to comply with the treatment program laid out by their psychiatrist. Dan was offered the stay if he would enroll in the CAFE clinical trial [Comparison of Atypicals in First Episode] in which he would be randomized to take either Seroquel, Zyprexa, or Risperdal. The absurdities were everywhere. He had been declared unable to "make decisions regarding his treatment," yet he was allowed to sign a consent form to be in the study. It was a maintenance study yet Dan had not responded. And he had written those notes above. After a few weeks, he was transferred to a halfway house that hardly addressed his lethality. The outcome parameter of the study was how many patients voluntarily discontinued the medication, yet Dan was court ordered to take the medication as a condition of his stay of commitment.
The treating physician was blinded to his medication, and the protocol didn’t allow for change of medication or dosage – hardly consistent with the needs in this case. Throughout the winter, Dan’s illness persisted and his mother mounted a campaign to get him out of the study without success. In the Spring, Dan killed himself violently with a box cutter leaving a bizarre note, "I left this experience smiling!" [see Carl Elliot’s, The Deadly Corruption of Clinical Trials for a more comprehensive history].
Everything’s wrong with this case. The CAFE study was an AstraZeneca experimercial conceived to counter Seroquel’s poor showing in the NIMH CATIE study. The rigid design didn’t allow the flexability needed in treating first episode psychotic illness, particularly one like Dan’s. Dan was no candidate for the trial on any count for obvious reasons, not the least of which was being required to take a medication in a study measuring patients’ rate of voluntary discontinuation of medication. He’s the kind of case where non-response to a first choice of medication would’ve dictated trying others, adding anxiolytics [forbidden by CAFE protocol], and considering a drug reserved for refractory psychosis. While there’s no guarantee that he would’ve responded, this is the kind of dire mental illness that calls for careful and vigorous treatment, not an unnecessary, fixed treatment, blinded clinical trial.
Carl Elliot, a bioethicist, has mounted a campaign to have this case investigated, so far without success. Most who hear the story or read the book, are horrified by what happened, but it has never become the expected cause célèbre in spite of a herculean effort by Carl and Dan’s friends and family. I have a speculation about why it hasn’t caught on, ignited the fire it deserves. My speculation is based on my own internal response to the case. I think Dan’s care was outrageous, and reaches to the heart of doing clinical trials for pharmaceutical marketing rather than to answer genuine scientific questions. I question whether the trial should’ve been done at all. In the case where it was done, I’m sure that Dan didn’t belong in it. And I can’t get around thinking that his being enrolled was to meet recruitment goals. Had he chosen to stop the medication [the outcome parameter], he faced "recommitment," something he didn’t want. His mother’s desperate attempts to withdraw him were ignored.
But I haven’t written much about it myself, at least as much as I would’ve expected given how I feel about it. I know he shouldn’t have been put into that study, We all know that. I think I’ve been inhibited because what I really think is that he should have been committed involuntarily for as long as it took to treat his severe psychosis. What I think is that in this case, antipsychotic medication should have been pursued vigorously in an effort to get his psychosis under control. What I think is that Benzodiazepines are often important adjuncts in such cases even with their addictive potential. What I think is this is the kind of case where considering the potentially toxic antipsychotic, Clozaril, with careful monitoring would be appropriate. And what I think is that Dan had a Disease. These are not popular things to say, and when I mention them, the comments often fill up with accusations and reminders of the psychiatric abuse of power, and I become the enemy to people whose views I often share. I felt a cringe even writing this paragraph. That probably shouldn’t bother me, but…
So I wonder if Carl Elliot has had difficulty engendering the kind of support he deserves and needs because this case stirs up such conflicted feelings in all of us, feelings that reach into the essential core of ethics – as his title implies, fear and loathing in bioethics. Ethics are easy when they’re simplified and you’re carrying a banner of truth, justice, and the American way. But they become hard when one is filled with opposing forces and conflicting motivations as is often the case in clinical medicine. I genuinely believe what I said in the last paragraph is the ethical approach to a paranoid, potentially violent, psychotic patient like Dan. In many other psychotic patients, I think an environment with the least possible restraint and the conservative use of medications is the ethical approach. The ethic is determined by careful attention to the human being in front of us, not by an ideology or some general treatment guideline or algorithm, certainly not by the marketing needs of a drug manufacturer. I’m absolutely sure that including a dangerously ill person needing a flexible vigorous treatment approach in a rigid, superfluous, blinded clinical trial is, by definition, unethical and deserves the most thorough investigation.