Opinion: Secular Trends and Postgraduate Teaching Challenges in Psychopharmacology

Abstract

Much has changed in the past two decades in terms of the pharmacotherapy of psychiatric disorders across the lifespan. It was just over 20 years ago that fluoxetine was first marketed in the United States and shortly thereafter clozapine made its remarkable return to patient care. But at the time these medications received marketing approvals from the FDA, Health Canada, and other nations’ regulatory agencies, we were not to know the impact they would have—on clinical practice, the pharmaceutical industry, psychotropic drug research, drug nomenclature, psychiatric nosology, perceptions of psychiatric patients and care, as well as education in clinical psychopharmacology. Prozac® quickly became a household word, supplanting Valium® as the best known psychotropic (Kramer, 1993). It also emerged as a lightning rod in child and adolescent psychopharmacology (Healy, 2003; Teicher et al., 1990). Prozac® was the first of several very successfully marketed SSRIs, which were found to be particularly effective in pediatric anxiety disorders. However, this therapeutic advance was overshadowed by these SSRIs’ uncertain benefit in adolescent depression and the early indications that they could promote rather than thwart suicidality in young patients (Research Unit on Pediatric Psychopharmacology, 2001; Kutcher & Gardner, 2008). The “awakenings” of chronically psychotic patients treated with clozapine generated hope and renewed interest in psychiatric practice, not unlike the pride described by psychiatrists 30 to 40 years earlier when the benefits of lithium, chlorpromazine, iproniazid, and imipramine were serendipitously uncovered, and heralded the modern psychopharmacologic era (Duckworth et al., 1997; Lambert, 1998). It was much easier to teach (and to learn) about psychotropic drugs when our understanding of the pathophysiological processes of mental illness were simple and the proposed mechanisms of how these drugs worked were uncomplicated. It was also easier to teach about psychotropics when their numbers were limited to a few distinct families with simply described pharmacological actions—dopamine antagonism for schizophreina, dopamine agonistic effects for attention, GABAmimetics for anxiety, and enhancement of serotonin or norepinephrine for depression. For bipolar disorder, we seemed content to have found lithium and other so-called mood stabilizers, even if their mechanisms remained mysterious. Never mind that the above psychotropic drugs were incompletely effective for most patients and completely ineffective for some, the proposed pharmacologic mechanisms meshed well with the pathophysiological proposals (though in many cases this was no coincidence) and this suited us just fine (Teicher, 1988). The neuroscientific basis of psychiatric disorders and investigations into the pharmacological effects of their treatments have exploded in the past 20 years coincident with advances in molecular genetics, molecular and cell biology, molecular pharmacology, pharmacogenomics, and imaging technologies. New findings have revealed the initial biologic theories of psychiatric disorders to be overly simplistic, incomplete, or wrong. However, replacing these aging theories with newer, widely accepted ones has not occurred despite many dramatic advances (Conn & Roth, 2008). Exemplifying the growth in this area and its complexity are the contents of the American College of Neuropsychopharmacology’s exhaustive 2002 reference text Neuropsychopharmacology 5th Generation of Progress. This text has 2,010 pages, written by almost 300 expert contributors, covering 134 chapters (Davis et al., 2002). In contrast to these neuroscience advances, new drug discovery has been slow and disappointing. It is sobering to note that the most commonly prescribed psychotropics share the same mechanism of action discovered many decades earlier. For example, olanzapine, risperidone, and quetiapine are more potent antagonists at 5-HT2 compared to D2, an effect of clozapine which was developed in 1961; venlafaxine’s dual reuptake blockade of serotonin and noradrenaline is a characteristic of the tricyclic antidepressants, and the specificity for serotonin reuptake inhibition was first observed with zimelidine in 1977 but was hardly a new mechanism of antidepressant action even then (Conn & Roth, 2008). Paradoxically, as the research base has expanded there seems to be less emphasis on teaching the neuroscientific basis of psychiatric disorders and their treatments. That is, as the information has become increasingly complex the response has been to de-emphasize its importance.