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Neuropsychopharmacology: Are We Ready for a Paradigm Shift? Roger E

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Neuropsychopharmacology: Are We Ready for a Paradigm Shift? Roger E ELSEVIER Neuropsychopharmacology: Are We Ready for a Paradigm Shift? Roger E. Meyer, M.D. The "paradigm shift" in the title of this article refers to and recent data suggesting that chronic exposure to molecular biology. The real challenge to molecular biologists addictive drugs results in changes in gene expression in interested in applying their methods to an understanding of neurons from behaviorally relevant brain regions, addictive psychiatric disorders involves the development of models disorders offer a serendipitous model (to molecular that account for gene/environment/development biologists) that may have relevance to subsequent interaction. Because of the existence of homologous animal application in other areas of psychiatry and psychology. models of addictive disorders, as well as a rich body of [Neuropsychopharmacology 14:169-179, 1996] clinical observations and clinical and behavioral research, KEY WORDS: Addictive disorders; Alcoholism; Molecular increase our understanding of the etiology of major and cellular biology; Animal models; Craving; Dopamine; mental illness. Has psychopharmacology represented a Nucleus accumbens scientific revolution, or has it simply served as an effec­ In December 1964, 18 months before the end of my psy­ tive challenge to the predominant psychoanalytic para­ chiatric residency, I attended my first American College digms that still held sway into the 1970s: Because of Neuropsychopharmacology (ACNP) meeting as the dynamic psychiatry saw psychopathology as "func­ guest of Dr. Alberto DiMascio. The meeting had a pro­ tional" for patients, its paradigm could not easily incor­ found and lasting impression on me. Psychopharmacol­ porate psychopharmacology and other somatic treatments ogy offered not only the promise of improved patient aimed at treating "dysfunctional" cognition, emotion, outcome, it also offered the promises of new under­ and behavior. Psychopharmacology undermined the standing of the pathophysiology of major mental disor­ validity and usefulness of psychodynamic explanations ders. There is no question that psychopharmacology of the etiology of mental disorders, but it has not yet launched a revolution in the clinical care of patients and resulted in a new paradigm to explain those disorders. in the development of new methods for the evaluation In his classic text, The Structure of Scientific Revolu­ of treatment. After more than 30 years, the question still tions, Kuhn (1970) highlighted the scientific develop­ remains whether it has begun to fulfill its promise to ments in the "hard sciences" associated with the names of Copernicus, Newton, Lavoisier, and Einstein. Each was associated with the rejection of an earlier theory, in From the George Washington University Medical Center, Wash­ favor of one that was not compatible with it. Each pro­ ington, DC. An earlier version of this paper was delivered at the Annual duced a shift in the problems available for scientific Meeting of the American College of Neuropsychopharmacology by scrutiny-and the requirements of evidence. Kuhn de­ Roger E. Meyer, Past President, in San Juan, Puerto Rico, December veloped the concept of "paradigms" and "paradigm 14, 1994, as his Plenary Address. Address correspondence to: Roger E. Meyer, M.D., Vice Presi­ shifts" (scientific revolutions). "Real science" is based dent for Medical Affairs/Executive Dean, George Washington Uni­ on "shared paradigms" that bring together the same stan­ versity Medical Center, 2300 Eye Street, N.W., Suite 713, Washington, dards and rules of scientific practice. "In the absence of DC 20037. Received December 30, 1994; revised March 29, 1995; accepted a paradigm or some candidate for a paradigm, all of the April 26, 1995. facts that could possibly pertain to the development of NEUROPSYCHOPHARMACOLOGY 1996-VOL. 14, NO. 3 © 1996 American College of Neuropsychopharmacology Published by Elsevier Science Inc. 0893-133X/96/$15.00 655 Avenue of the Americas, New York, NY 10010 SSDI 0893-133X(95)00074-N 170 R.E. Meyer NEUROPSYCHOPHARMACOLOGY 1996-VOL. 14, NO. 3 a given science are likely to seem equally relevant." digms must account for observations that cannot be Moreover, "in the absence of a reason for seeking some explained with existing models but new paradigms are particular form of information, . fact gathering is also the source of new methods, new problem fields, restricted to the wealth of data at hand" (Kuhn 1970, and new standards of acceptable solutions. "The recep­ p. 15). tion of a new paradigm often necessitates a redefinition This audience should have no difficulty recognizing of the corresponding science" (Kuhn 1970, p 103). the paradigm shift that occurred in the 17th century. During my 30 years of participation in the meetings Prior to that time, the Aristotelian model opined that of the ACNP, we have been offered a marvelous inter­ "an object falls because its 'nature' drives it toward the disciplinary forum and multidisciplinary membership center of the universe" (Kuhn 1970, p 104). When clini­ through the era that focused on neurotransmitter-based cal psychopharmacology challenged this type of tauto­ models of pathophysiology. But the self-study activity logical reasoning in academic psychiatry, the field that we began last year revealed a discomfort among returned to the traditions of descriptive psychiatry with some of our members with the growing influence of the notion that greater diagnostic specificity would lead molecular neurobiology (and molecular neurobiologists) to a more rational pharmacotherapy-and a greater within the ACNP. This angst was also reflected in the likelihood of linking psychopharmacology to an increased efforts by some of our members to establish the Ameri­ understanding of pathophysiology. Although the "jury" can Society of Clinical Psychopharmacology and to must still be considered to be "out" regarding the valid­ challenge the Program Committee, the Credentials Com­ ity of this assumption, the efficacy of some antidepres­ mittee, and the leadership of our society regarding the sants in the treatment of mood disorder, panic disorder, continuing relevance of our organization to clinical psy­ obsessive-compulsive disorder, and some eating disor­ chopharmacology. There seemed to be real concern ders would appear to argue against a strong case for about the amount of molecular biology on the program drug/ disorder specificity (based on current nosology and the numbers of molecular biologists approved for and criteria) as the "royal road" to understanding patho­ membership in the ACNP. physiology. Indeed, Kuhn would probably recognize Molecular biology has presented a challenge to our this period in our field's history as being notable for the membership, much as it has confronted the corpus of absence of a paradigm-an observation that seems to be pharmacology as a discipline. As we know, some medi­ reinforced by the many diagnostic categories and heter­ cal schools have even dropped pharmacology as a dis­ ogeneous criteria within the three successive volumes tinct department and the old departmental boundaries of diagnostic and statistical manuals of the American across the basic sciences of biochemistry, physiology, Psychiatric Association over the past 15 years. Using and pharmacology have fallen in the face of the emerg­ analogies from the "hard sciences," he would regard this ing paradigm shift offered by molecular biology. Will period, although scholarly, as pre-scientific. "To reject one neuropsychopharmacology be submerged in the new paradigm without simultaneously substituting another molecular neurobiology? What can molecular neurobi­ is to reject science itself" (Kuhn 1970, p 79). The discov­ ology mean to us as a discipline? Is there no way to rec­ ery of digitalis improved the treatment of some patients oncile the explicit reductionism of the emerging paradigm with edema, but the descriptive literature on the varie­ with the multivariate complexity of our data? Are we ties of dropsy continued. ready for the revolution that is affecting the rest of med­ Developments in psychopharmacology have led to a icine? Will molecular biology offer us the unifying para­ variety of new theories of mental disorder, which have digm that our field has lacked since the introduction of seemed consistent with the purported mechanisms of the first antidepressants, anxiolytics, and neuroleptics action of psychoactive drugs. When Heinz Lehmann challenged the usefulness of psychoanalysis as an explan­ commented about "life's depletions" at an ACNP meet­ atory model of psychopathology and its treatment? ing in the 1970s, there was an understandable metaphoric During the past 15 years, each report of genetic link­ linkage between a theoretical deficiency of norepineph­ age of major mental illness has been followed by a fail­ rine in the synapse, the acute effects of known antide­ ure to replicate. The highs and lows that have greeted pressants, and the depleted persona of melancholia. But these reports in our literature have raised doubts with the introduction of each new drug class of antide­ among geneticists about the readiness of our syndromal pressant and the recognition that acute drug effects did models for 21st century biology. Our genetic models not account for the temporal realities of recovery have presumed a deterministic connection between a through medication, one theory replaced another. Even faulty gene and the syndromes defined by the DSM's with our growing knowledge base of receptor subtypes since 1980, whereas
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