Barry Blackwell: Adumbration: A History Lesson

       Andre Veras is the first colleague to comment on this essay and does so with pertinent and intriguing insights and some memorable phrases, raising issues that invite further discussion.

       He asserts that new discoveries of the kind I describe are today more likely in areas of “high technology in well stabilized research centers” but also implies that psychiatry is still a clinical arena where a beginner “with the privilege of unacquainted eyes” might discover something novel. I agree that curiosity and naiveté are important ingredients and that new fields are more likely to yield fresh findings. Some pioneers in the Oral History of Neuropsychopharmacology commented on the reinforcing effects of working in an environment where everything was new and often statistically significant.

       At the same time, technology can exert an inhibiting influence. Many clinicians bemoan the contemporary absence of bedside teaching in history taking, clinical examination and diagnosis with early resort and undue reliance on laboratory tests and imaging studies, diverting eyes away from the patient and their concerns.

       The contemporary example I cited of sudden onset hypertension provoked by a Cox 2 inhibitor for arthritic pain raises a relevant question. How could Vioxx have been taken by 20 million Americans, an estimated 88,000 of whom suffered heart attacks and 8,000 died before it was withdrawn? How many young doctors who cared for these patients must have heard their complaints or witnessed their distress without making a connection to the treatment or not reporting it if they did?

      Several factors are probably in play, some briefly alluded to in the essay, but worthy of elaboration. We live in an era when television advertising (permitted only in the USA and New Zealand) creates a Pollyannaish picture of drugs, in which known side effects are mentioned but drowned out and evicted from memory by distracting imagery. In this atmosphere, curiosity is dulled or even extinguished, obliterating cause and effect concerns on the part of patients and physicians if an untoward event occurs.

       When I reported my own experience to the pharmaceutical company and the FDA, the former gave me bland and inaccurate reassurances and the latter was silent. Fifty years ago, the pharmaceutical representative was encouraging about cheese and the company started their own research (although they did try to steal priority of publication, foiled by a Lancet editor).

       The influence of money generated by “blockbuster drugs” has become more powerful and pervasive, corrupting industry and academia. The cost of denying, litigating and eventually compensating for life threatening side effects is built into the high cost of new medication and sequestered as “the price of doing business.”  When a “black box” warning is eventually mandated by the FDA, the burden of liability now rests with the physician who prescribes and the patient who ignores it. The manufacturer remains unaccountable and profitable.

       Worse yet, testing of new psychotropic drugs is almost entirely in the hands of industry, often including research design, statistical analysis, write up and decisions about publication. Independent analysis and dissemination of the results before and after marketing by clinical guideline panels, professional organizations, conferences, medical educators and FDA panels is often tainted by conflicts of interest generated by generous grants, stipends and fees for advisory functions, lectures, conferences, endorsements or serving on committees; all willingly provided by influential academics. These conflicts are disclosed but never assessed or examined for evidence of influence, the lack of which is optimistically assumed. (See “Conflict of Interest” in Controversies on INHN).

       Residents aspiring to an academic career assume the “publish or perish” burden, which is more difficult to accomplish now, especially for neophytes reporting a serious side effect. Journals have become dependent on pharmaceutical advertising and editors are cautious about their revenue source as well as fear they may incur liability or blame for endorsing or prior publications concerning the drug.

       Andre was taught, just as I learned, that the “original” ideas we espouse have almost always been voiced before, but often in a different framework. This is why it is incumbent on pharmaceutical company scientists to be diligent and held accountable for researching the history and diverse properties of drugs they seek to market, avoiding a commercially driven focus on a single indication or mode of action.

       Finally, Andre makes a similar point related to the benefits of translational dialog, “bringing knowledge from one field to another.” Here there is also cause for concern. When the ACNP was founded over 60 years ago, this was a core principle well served by a balance in membership between clinicians active in human research and neuroscientists working mostly in animals. Despite the fact that more members now have joint degrees (M.D. and Ph.D.), the balance has tilted to one side, brought about by the virtual exit of NIMH from support for clinical research of the type once conducted by the NCDEU Program and the hegemony of an industry driven more by profit than science. The ratio of meaningful translational findings to the number of posters and their multiple authors on display at ACNP annual meetings is hardly encouraging.

Barry Blackwell

October 22, 2015