Thomas A. Ban
Neuropsychopharmacology in Historical Perspective
Education in the Field in the Post-Neuropsychopharmacology Era
Overview of the series
An Oral History of Neuropsychopharmacology
(Educational Series 2. Bulletin 3. Vignette 1)
This is an extract of the “Overview of the series” printed in Volume One of An Oral History of Neuropsychopharmacology The First Fifty Years Peer Interviews, a 10-volume series, edited by Thomas A. Ban, published by the American College of Neuropsychopharmacology, in 2011.
Overview of the series
The field of neuropsychopharmacology is now more than a half-century old. In the 1990s the American College of Neuropsychopharmacology began an interviewing program to draw on the memories of the American pioneers. The collection of 238 interviews, presented in this 10-volume series, is a resource for historians of neuropsychopharmacology of the future, and also a source of enlightenment and inspiration for scientists and clinicians today.
It was the therapeutic and commercial success in the mid-1950s of chlorpromazine for the treatment of schizophrenia that generated interest within the pharmaceutical industry in developing drugs for other psychiatric conditions (Ban 2007). By the end of the 1950s there were several effective drugs in clinical use for the treatment of psychosis, depression and anxiety. The psychiatric establishment received the new drugs incredulously. Yet with the help of the pharmaceutical industry, by the end of the 1950s, pharmacotherapy with psychotropic drugs had become an accepted treatment modality, and psychopharmacology had become part of the teaching curriculum at medical schools (Ban and Ucha Udabe 2006).
The term “psychopharmacology” was introduced in 1920 by David Macht, an American pharmacologist at Johns Hopkins University, for describing the effects of the antipyretics, quinine and acetylsalicylic acid on neuromuscular coordination tests (Macht 1920). The term was used as a synonym for “pharmacopsychology,” a term introduced in 1892 by Emil Kraepelin, for describing the “psychic effects” of morphine, alcohol, paraldehyde, chloral hydrate, ether and amyl-nitrate (Kraepelin 1892). The scope of psychopharmacology was gradually extended to all experimental investigations of the psychometric and “psychic” effects of drugs. By the 1940s, with the availability of lysergic acid diethylamide, psychopharmacology embraced research with psychotomimetics (also referred to as hallucinogens, psychodysleptics, psychotopathics, etc.), and by the 1950s it included clinical investigations of the therapeutic effects of a rapidly growing number of new psychotherapeutic drugs used in the treatment of psychiatric disorders (Ban 2004). Simultaneously, with the availability of effective psychotropic drugs in mental illness, such as chlorpromazine, reserpine, imipramine, and iproniazid, there was a shift in the understanding of the nature of synaptic transmission from a purely electrical to a chemically mediated event; by the end of the 1950s seven neurotransmitters had been identified in the central nervous system: acetylcholine, epinephrine, dopamine, γ-amino butyric acid, norepinephrine, serotonin, i.e., 5-hydroxytryptamine, and substance P (Ban 2006). Recognition of chemical mediation at the site of the synapse, coupled with the introduction of the spectrophotofluorometer (Bowman, Caulfield and Udenfriend 1955), an instrument with a resolution power to detect drug-induced changes in the concentration of neurotransmitter monoamines and their metabolites, led to the development of neuropharmacology, a branch of pharmacology that deals with the detection and identification of structures responsible for the psychotropic effects of centrally acting drugs. Previously, research dealing with centrally acting drugs was restricted to behavioral pharmacology (Simon 1998) and neurophysiological measures. Spectrophotofluorometry provided direct access to the detection of the biochemical changes that might be responsible for therapeutic effects. Spectrophotofluorometry has also opened the path for the development of neuropsychopharmacology, a new discipline that studies the relationship between neuronal and mental processing in the brain with the employment of centrally acting drugs (Ban 2004).
The first neuropharmacological studies with the aid of spectrophotofluorometry revealed: (1) that administration of reserpine, a Rauwolfia alkaloid, produced a decrease in brain serotonin and norepinephrine levels (Holzbauer and Vogt 1956; Pletscher, Shore and Brodie 1955); (2) that administration of iproniazid, an inhibitor of the enzyme responsible for the breakdown of monoamines (Zeller, Barsky, Fouts, et al. 1952), increased brain serotonin levels (Pletscher 1956); (3) that pre-treatment with iproniazid attenuated reserpine-induced depletion of serotonin and catecholamines (Besendorf and Petscher 1956; Carlsson, Rosengren, Bertler and Nilsson 1957); and (4) that only those Rauwolfia alkaloids (Brodie, Shore and Pletscher 1956) and benzoquinolizines (Pletscher 1957) (a group of synthetic substances) that depleted serotonin had tranquilizing, or sedating, action. A possible relationship between mood and cerebral monoamine levels was based on clinical reports which indicated that treatment with iproniazid induced euphoria, a feeling of well-being in some tubercular patients (Flaherty 1952; Selikoff, Robitzek and Orenstein 1957), whereas treatment with reserpine induced depressed mood or dysphoria in about 15% of hypertensive patients (Freis 1954; Muelle, Pryor, Gibbson and Orgain 1955). The “birth” of neuropsychopharmacology in the mid-1950s was the result of combining these clinical observations with findings in neuropharmacological research (Ban 2008). The foundation of the new discipline was tenuous. There were reports that isoniazid, the parent substance of iproniazid, had similar effects on mood to those of iproniazid without virtually any effect on monoamine oxidase activity (Delay, Laine and Buisson 1952: Salzer and Lurie 1953, 1955). There was also a report on the favorable effects of reserpine in anxious and depressed patients (Davies and Shepherd 1955; Healy 1997).
One of the first to recognize that neuropsychopharmacology opened up a new perspective in the understanding of psychiatric illness was Abraham Wikler, an American psychiatrist (Hollister 1996). In his monograph on The Relation of Psychiatry to Pharmacology, he suggested that studying the mode of action of psychotropic drugs with known therapeutic effects might provide information on the biochemical basis of mental disorders (Wikler 1957. By generating information on molecular changes in psychiatric illness, findings in neuropsychopharmacological research were to guide the development of rational drug treatments. The notion that drugs with known therapeutic effects might provide the key for bridging the gap between neuronal processing and mental pathology has remained the driving force for research in the new field.
By the end of the 1950s, the “neurotransmitter era,” the first epoch in the history of neuropsychopharmacology had taken form. Research in the pathophysiology and treatment of mental illness had become guided by knowledge derived from the effect of psychotropic drugs on neurotransmitter dynamics and metabolism (Pletscher 2006). In the 1960s neuronal re-uptake and pre-synaptic mechanisms became the focus of interest. Yet, as time passed, attention shifted to receptors and post-synaptic mechanisms. In the late 1970s the scope of research was extended from cerebral monoamines to neurotransmitter modulators, neuropeptides and prostaglandins (Carlsson 1986). With the recognition in the mid-1980s that communication in the brain is not restricted to “wiring transmission” (based on neurotransmitter dynamics) in which one neuron connects directly with another, but also involves “volume transmission” that takes place in the extra-cellular space (Agnati, Fuxe, Zoli, et al. 1986), the neurotransmitter era was approaching its end. Yet it was only after the introduction of molecular genetic technology in the 1990s that a genetic era in neuropsychopharmacology emerged (Ban and Ucha Udabe 2006).
During its first 50 years neuropsychopharmacology had a major impact on the development of psychiatry. The site of psychiatric practice shifted from the psychiatric hospital to the community; the scope of psychiatry was extended from the psychoses and neuroses to dimensional anomalies of abnormal psychology; and pharmacological therapy has come to dominate treatment in most psychiatric disorders. By supplying drugs with demonstrated therapeutic efficacy, together with information on their mode of action in the brain, the pharmaceutical industry had played an important role in changing the thinking of psychiatrists from psychological to biological and reintegrating psychiatry with the other medical disciplines (Ban 2006).
Recognition of the need in research for continuous dialogue between clinicians and basic scientists resulted in the founding of associations that would provide a platform for interaction among the various disciplines of the new field. The first major organizations to provide such platforms were the Collegium Internationale Neuro-Psychopharmacologicum (CINP), founded in 1957 (Ban 2006), and the American College of Neuropsychopharmacology (ACNP), founded in 1961 (Ray 2004). Both the International and the American organizations have also offered a venue for communicating information about new psychotropic drugs. With the support of the US Public Health Service and the pharmaceutical companies, by the mid-1960s research in neuropsychopharmacology flourished in the United States. The annual meetings of the American College of Neuropsychopharmacology were to become signposts in the development of the discipline.
By the mid-1990s the pioneer generation was fading away; to preserve their legacy, the late Oakley Ray, at the time ACNP’s Secretary, generated funds from Solway Pharmaceuticals for the founding of the ACNP-Solway Archives in Neuropsychopharmacology. Ray also arranged for the videotaping of peer-interviews with the pioneers at annual meetings, to be stored at the archives. The endeavor that was to become known as the “oral history project” was gradually extended to include videotaped interviews with members of the College, and later also with non-members, who contributed to the development of the field. Most of these interviews were conducted by peers. Furthermore, with ACNP’s 50th Anniversary approaching in 2011, a few special interviews were videotaped with a focus on the history of the college and on interviewees’ contributions to the activities of ACNP.
In this series of 10 volumes the edited transcripts of these biographical interviews collected over a period of 14 years (from December 1994 to December 2008) are presented. The material is based on 235 videotaped interviews conducted by 66 interviewers – most of them peers, knowledgeable in the same field of inquiry – with 213 interviewees who contributed to the development of neuropsychopharmacology. Of the 235 interviews, 212 were done at ACNP’s annual meetings and 23 between meetings; 229 involved a single interviewer, five involved two interviewers and one was a group interview. Some interviewees were the subjects of several interviews.
The series covers the first 50 years in the history of neuropsychopharmacology. Volume 1 deals with the state of the art in psychiatry and pharmacology at the time of the emergence of neuropsychopharmacology; and Volumes 2 through 8 with various areas of research, clinical activities and education in the discipline. Volume 9 is focused on the changes over the years and Volume 10 on the history of ACNP. The transcripts of Volumes 1 through 8 are based on first interviews and of Volume 9 on second (update) interviews. Volume 10 includes, in addition to interview transcripts, material relating to the history of ACNP excerpted from transcripts presented in prior volumes. Introductions by some of the volume editors provide an overview of developments in the particular area within neuropsychopharmacology covered in that volume, and a Preface by the series editor draws together the contributions presented in the various volumes into a history of the field as a whole. Volume 10 also includes a Postscript to the Series by the series editor outlining the present status of neuropsychopharmacology; a Quotation selected from each interview; a Chronological List of Publications in neuropsychopharmacology based on interviewees contributions and references in editor’s Preface in the volumes; and Acknowledgements of the numerous contributors to this project, which has taken more than 16 years to reach fruition.
In the information overload created by the online accessibility of virtually all information that is not protected by patent or copyright, authentic primary sources are often indistinguishable from inaccurate or trivial information. By presenting the first-hand accounts of ACNP members about their contributions to the field, this series provides a guide to recover the historical record from the flood of non-replicable research reports and time-bound reviews contaminated by reviewers’ biases. It complements David Healy’s three-volume series (The Psychopharmacologists) which includes the edited transcripts of audiotaped interviews with 78 psychopharmacologists selected for their significant contributions to the development of the field (1996, 1998, 2000). It complements as well CINP’s four-volume series (The History of Psychopharmacology and the CINP, As Told inAutobiography), which includes the autobiographical accounts of about 250 leaders of psychopharmacology from more than 50 countries (Ban, Healy and Shorter 1998, 2000, 2002, 2004). These three series of source books offer historians reliable material for reconstructing the early history of neuropsychopharmacology. The original videotapes will be available in ACNP’s International Archives in Neuropsychopharmacology.
Agnati LF, Fuxe K, Zoli M, Zini I, Toffano G, Ferraguti F. A correlation analysis of regional distribution of central enkephalin and ß-endorphin immunoreactive terminals and of opiate receptor in adult and old male rats. Evidence of the existence of two main types of communications in the central nervous system: The volume transmission and the wiring transmission. Acta Physiol Scand 1986; 128: 201–7.
Ban TA. Neuropsychopharmacology and the history of pharmacotherapy in psychiatry. A review of developments in the 20th century. In: Ban TA, Healy D, Shorter E, editors. Reflections on Twentieth-Century Psychopharmacology. Budapest: Animula; 2004. p. 697–720.
Ban TA. Academic psychiatry and the pharmaceutical industry. Prog Neuropsychopharmacol Biol Psychiatry 2006; 30: 429–41.
Ban TA. A history of the Collegium Internationale Neuro-Psychopharmacologicum (1957–2004). Prog Neuro-Psychopharmacol Biol Psychiatry 2006; 30: 599–616.
Ban TA. Fifty years chlorpromazine. A historical perspective. Neuropsychiat Dis Treat 2007; 3: 483–8.
Ban, T.A. The birth of neuropsychopharmacology. Neuropsychopharmacol Hung 2008; 3 (Suppl 2): S12–3.
Ban TA, Healy D, Shorter E, editors. The Rise of Psychopharmacology and the Story of CINP. Budapest: Animula; 1998.
Ban TA, Healy D, Shorter E, editors. The Triumph of Psychopharmacology and the Story of CINP. Budapest: Animula; 2000.
Ban TA, Healy D, Shorter E, editors. From Psychopharmacology to Neuropsychopharmacology in the 1980s and the Story of CINP. Budapest: Animula; 2002.
Ban TA, Healy D, Shorter E, editors. Reflections on Twentieth-Century Psychopharmacology. Budapest: Animula; 2004.
Ban TA, Ucha Udabe R. The neurotransmitter era in neuropsychopharmacology. In: Ban TA, Ucha Udabe R. editors. The Neurotransmitter Era in Neuropsychopharmacology. Buenos Aires: Polemos; 2006. p. 265–74.
Besendorf H, Pletscher A. Beeinflussung zentraler Wirkungen von Reserpin und 5- Hydroxytryptamin durch Isinicitinsaurehydrazide. Helv Physiol Pharmacol Acta 1956; 14: 383-90.
Bowman RL, Caulfield PA, Udenfriend S. Spectrophotometric assay in the visible and ultraviolet. Science 1955; 122: 32–3.
Carlsson A. The 12th CINP Congress. In: Ban TA, Hippius H, editors. Thirty Years CINP. Berlin: Springer; 1986, p. 42–3.
Davies DL, Shepherd M. Reserpine in the treatment of anxious and depressed patients. Lancet 1955; 2: 117–20.
Delay J, Laine B, Buisson JF. Note concernant l’action de l’isonicotinyl dans le traitement des états dépressives. Ann Med Psychol (Paris) 1952; 110; 689–92.
Freis ED. Mental depression in hypertensive patients treated for long periods with large doses of reserpine. N Engl J Med 1954; 251: 1006–8.
Healy D. The Psychopharmacologists. Interviews by David Healy. London: Altman; 1996.
Healy D. The Antidepressant Era. Cambridge: Harvard University Press; 1997. p. 72–4.
Healy D. The Psychopharmacologists II. Interviews by David Healy. London: Altman; 1998.
Healy D. The Psychopharmacologists III. Interviews by David Healy. London: Arnold; 2000.
Hollister LE. Review of Wikler’s The Relation of Psychiatry to Pharmacology. In: Ban TA, Ray OS, editors. A History of the CINP. Nashville: JM Productions; 1996. p. 339–43.
Holzbauer M, Vogt M. Depression by reserpine of the noradrenaline concentration in the hypothalamus of the rat. J Neurochem 1996; 1: 8–11.
Mueller JC, Pryor WW, Gibbons JJ, Orgain ES. Depression and anxiety occurring during Rauwolfia therapy. JAMA 1955; 159: 836–9.
Kraepelin E. Über die Beeinflussung einfacher psychischer Vorgänge durch einige Arzneimittel. Jena: Fischer; 1892.
Macht DL. Contributions to psychopharmacology. Bull Johns Hopkins Hosp 1920; 31: 167–73.
Pletscher A. The dawn of the neurotransmitter era in neuropsychopharmacology. In: Ban TA, Ucha Udabe R, editors. The Neurotransmitter Era in Neuropsychopharmacology. Buenos Aires: Polhemos; 2006. p. 27–37.
Pletscher A. Beeinflussung des 5-Hydroxytryptamin-stoffwechsels im Gehirn durch Isonikotinsäurehydrazide. Experientia 1956; 12: 479–80.
Pletscher A, Shore PA, Brodie BB. Serotonin release as a possible mechanism of serotonin action. Science 1955; 122: 374–5.
Ray OS. The history of the American College of Neuropsychopharmacology. In: Ban TA, Healy D, Shorter E, editors. Reflections on Twentieth-Century Psychopharmacology. Budapest: Animula; 2004. p. 616–20.
Salzer HM, Lurie ML. Depressive states treated with isonicotinyl hydrazide (isoniazid). Ohio State Med J 1955; 51:437–41.
Salzer HM, Lurie ML. Anxiety and depressive states treated with isonicotinyl hydrazide (isoniazid). Arch Neurol Psychiatry 1953; 70: 317–24.
Simon P. Behavioural pharmacology. In: Ban TA, Healy D, Shorter E, editors. The Rise of Psychopharmacology and the Story of CINP. Budapest: Animula; 1998. p. 131–4.
Wikler A. The Relation of Psychiatry to Pharmacology. Baltimore: Williams and Wilkins; 1957.
Zeller EA, Barsky JR, Fouts W, Kirchheimer WP, Van Orden LS. Influence of isonicotinic acid hydrazide (INH) and 1-isonicotinyl-2-isopropyl hydrazide (IIH) on bacterial and mammalian enzymes. Experientia 1952; 8: 349–50.
February 1, 2018