I’d like to comment further on the issue of Deep Brain Stimulation (DBS), partly to clarify a couple of issues I should have addressed at more length in my last post, and partly to draw attention to a deeply alarming example of experimentation on patients that surfaced in the Washington Post this week.
The recent report on DBS published in the American Journal of Psychiatry this month was an open, unblinded study undertaken in the aftermath of a catastrophically bad clinical trial that was blinded. Not only did that trial (and another parallel trial sponsored by a competing medical device manufacturer) fail to show any efficacy in treatment-resistant depression, it exposed the participants to a range of extremely serious, even life-threatening complications. Undaunted, Helen Mayberg and her colleagues running her failed trial left the devices in place in the patients who could tolerate them, and continued to stimulate their brains.
Because of the massive conflicts of interest that plague academic medicine, some years back medical journals began to require that authors of papers declare financial ties that might call into question the independence of the authors’ assessment of the trials they were reporting on. These new rules have proved to be little more than a fig leaf, masking the ways in which sponsorship by interested parties leads to “findings” that are heavily biased.1 When comparisons are made between studies of drugs sponsored by Big Pharma, and trials sponsored by federal dollars, those with drug company sponsorship routinely report far more favorable results than studies where no commercial interests are at stake.2 The situation is even worse when it comes to medical devices. A study appearing last year in JAMA Surgery, “Association of Compensation from the Surgical and Medical Device Industry to Physicians and Self-Declared Conflict of Interest,” examined whether the 100 physicians receiving the highest compensation from 10 large surgical and medical device manufacturers actually declared their conflicts of interest. The results were deeply disturbing, though not surprising: Conflicts of interest were declared in only 84 of 225 relevant publications, or 37.3%. In other words, in nearly two-thirds of cases, these physicians lied, and of course they did so with impunity. So it is that “evidence-based medicine” becomes “evidence-biased medicine.”3
But serious problems exist even when possible conflicts of interest are “declared.” The relevant statements at the end of academic papers provide minimal detail, thus disguising the true extent of the conflicts that exist. If we know only that X received some grant support from company Y, we are left in the dark about the extent of this support. In the case of the recent American Journal of Psychiatry paper, not only were the authors indebted financially to the medical device manufacturer seeking to expand the market for its wares, but at least one of the authors, Helen Mayberg, owned patents covering the devices in question. Were results to be seen as favorable, the potential financial and career rewards for her (and for the others participating in the study) were extensive and readily overlooked by those reading her study, given the imprimatur of one of psychiatry’s two leading professional journals.
It should come as no surprise that, in the face of clear negative findings from two controlled trials, these authors were nonetheless tempted to continue to make a case for their experimental treatment, despite unimpeachable evidence of the harm suffered by many of their experimental subjects (as I summarized in my previous blog piece). That they should have been allowed to do so is a scandal. That an accompanying editorial in the American Journal of Psychiatry should laud them as examples of “rigorous clinical research efforts” and “outstanding examples of the efforts and dedication of researchers committed to helping clinicians successfully treat patients whose symptoms are not responsive to treatment” leaves one close to despair. The cherry-picked data in the paper by Mayberg et al. should give any moderately critical reader pause, and the fact that positive outcomes only appear when biased researchers are allowed to self-assess the results of their interventions is telling. And that is to leave aside the often extremely serious sequelae associated with this form of psychosurgery.
When I published a study of an earlier example of the desperate remedies to which mental patients have often been subjected (removal of teeth, tonsils, and internal organs as part of an attempt to extirpate the focal sepsis that was allegedly poisoning mental patients’ brains, killing hundreds and maiming thousands, an outcome covered up at the highest levels of the profession), I was often asked if something similar could happen today. My response, which present events vindicate, was that though history rarely repeats itself exactly as before, similar horror stories could not be ruled out. Mental patients remain extremely vulnerable. The etiological understanding of mental disorders remains strikingly primitive, and such treatments as we have provide at best a measure of symptomatic relief to a subset of these patients, often at a very heavy price in terms of side effects. Ambitious clinicians let loose in such a situation can easily be carried away by their enthusiasms, and the restraints on experimentation, while stronger than they once were, remain inadequate.
One further remark before I pass on to this week’s news: when lobotomy was introduced in the mid-1930s, it was popularized by a duo consisting of a neurologist (Walter Freeman) and a neurosurgeon (James Watts). The vogue for DBS is to some degree the result of the self-promoting activities of another duo, also a neurologist and a neurosurgeon. Both groups, of course, needed the active collaborations of some psychiatrists to advance their work, but the impetus came from outside psychiatry itself. And the work of the lobotomists and of the latest advocates of a deeply invasive neurosurgery was in both instances greeted by uncritical articles by science journalists who should have known better. I am constantly appalled by articles even in serious newspapers that breathlessly tout the latest medical “breakthrough” — based on an anecdotal study or two that proves precisely nothing.
Which brings me to this week’s example of the genre, which appeared in the pages of the November 6th issue of the Washington Post. A fascinating and immensely promising new treatment was being advanced as a breakthrough in the treatment of the scourge of opioid addiction. And what was this miraculous new intervention? Implanting electrodes deep in the brain, and using a battery implanted elsewhere in the body to zap the addict and keep him from relapsing.
The reporter regaled us with the story of a heroic neurosurgeon who implanted this device after seven hours of neurosurgery. It was, we were solemnly assured, akin to the medical miracle that is a heart pacemaker. This one was a brain pacemaker, rejiggering the functions of the brain. Think about that for a second — a heart pacemaker has a relatively simple, if vital, task to perform: causing the muscular pump that is one’s heart to maintain a steady beat in cases where it is prone to beat irregularly or too slowly. The human brain is not a pump.It is a fantastically complicated organ composed of about 200 billion nerves cells, interconnected in hundreds of trillions of ways. Despite all the progress of neuroscience over the past half-century, our understanding of how it is put together, and how all those myriad connections function, remains strikingly primitive. The idea of a “brain pacemaker” is so ludicrous on its face as to disqualify anyone who uses it. To accept such a bizarre analogy is to show oneself incapable of serious commentary on subjects of this sort. The same could be said of the notion of “precise” placement of devices within the brain, and of the sort of speculations about the localization of depression or addiction in particular regions of the brain that people like Helen Mayberg trot out to support their baseless experimentations.
Helen Mayberg, the inimitable Helen Mayberg, is, quelle surprise, the reporter’s go-to source for confirmation of how promising this new approach is likely to be. She duly obliges, claiming that “the logic of the effort is sound and that the circuitry of this part of the brain is well-mapped compared with other regions. The key question is whether the researchers have found the precise spot for the insertion of the electrodes. The precision of where you put it is key,” she said. “Different nodes are good for different kinds of problems because circuits are abnormal in different ways.” Alcoholics, spousal abusers, criminals, you’re next! For your behaviors too, one presumes, can be solved by implanting suitable brain pacemakers. And if they don’t work? Why, the surgeon put the damned thing in the wrong place. Sorry about that. As you will note, Dr. Mayberg has thereby provided herself with a wonderful get out of jail free card when addicts don’t recover.
The surgery the Post reporter focuses on is the first of four trial cases designed to establish that “the technique is safe so that a full-scale clinical trial can be conducted.” Let us set aside the fantasy of tens of thousands of opioid addicts being subjected to seven hours of psychosurgery (a nice fantasy for medical device makers to entertain). Let us set aside the parade of serious side effects that we know those in the controlled trials of DBS for depression suffered. What justifies the experiment? The surgeon in question is quoted as acknowledging that “doctors and researchers do not yet fully understand how this works” — a statement that should more accurately read: “we have not the slightest clue of how this might work.” The prattle about dopamine that he proceeds to utter as a substitute for the scientific evidence we do not possess is an embarrassment — just speculation plucked out of thin air. As for the “inspiration” to perform the surgery, it turns out it was anecdotal reports from China! The Director of the National Institute on Drug Abuse, Nora Volkow, “spoke with a handful of the patients who underwent the procedure in China and concluded that the surgery had potential.”
This is the quality of reasoning from the person who heads this major federal agency, and that guides what dangerous interventions are allowed on an experimental basis? Words fail me.
- For some discussion of this issue, see my Psychiatry and Its Discontents (University of California Press, 2019), 289-295. ↩
- See, for example, Joel Lexchin, Lisa Bero, Benjamin Djulbegovich, and Otavio Clark, “Pharmaceutical Industry Sponsorship and Research Outcome and Quality: A Systematic Review,” British Medical Journal 326, 2003, 1167-1170; Gisela Schott, Henry Pachl, Ulrich Limbach, Ursula Gundert-Remy, Wolf-Dieter Ludwig, and Klaus Lieb, “The Financing of Drug Trials by Pharmaceutical Companies and Its Consequences,” Deutsches Arzteblatt International 107, 2010, pp. 279-285; Andreas Lundh, Joel Lexchin, Barbara Mintzes, Jeppe Schroll, and Lisa Bero, “Industry Sponsorship and Research Outcome,” The Cochrane Database of Systematic Reviews 2, 2017, http://cochranelibrary-wiley.com/doi/10.1002/14651858.MR000033.pub3/abstract, accessed June 26, 2018. ↩
- JAMA Surgery 153, 2018, 997-1002. ↩