The PSYCHOPHARMACOLOGISTS 1
1 PIERRE PICHOT The Discovery of Chlorpromazine
Pichot was a senior figure in Jean Delay’s Department of Psychiatry when chlorpromazine was discovered. He later conducted important studies with haloperidol and clomipramine, championed clinical trial and statistical methodology in France and became Professor of Psychiatry in Paris. Internationally known for his work on the History of Psychiatry, he was a founder member of the Association for European Psychiatry.
2 JULIUS AXELROD The Discovery of Amine Reuptake
Axelrod began at the famous laboratory in Goldwater Memorial Hospital in which he, Steve Brodie and others laid the foundations for pharmacokinetics and pharmacodynamics before moving to the National Institutes of Health during a “Camelot” period, when Brodie and others were laying the basis for psychopharmacology. He was involved in the discovery of the microsomal enzyme system and amine reuptake mechanisms for which he won the Nobel Prize in 1970, that laid the basis for drugs like Prozac.
3 ARVID CARLSSON The Rise of Neuropsychopharmacology
Carlsson’s career began with early work with Steve Brodie at NIH. He was involved in the discovery of dopamine in the brain, in establishing the importance of chemical neurotransmission, in postulating dopamine might be deficient in Parkinson’s disease and that antipsychotics might act through the dopamine system. His work was seminal to the development of the serotonin reuptake inhibitors (SSRIs) and the first SSRI – zimelidine.
4 FRANK AYD The Discovery of Amitriptyline
Ayd helped found the first international psychopharmacology association, the CINP, and the American College for Neuropsychopharmacology (ACNP). He discovered the antidepressant effects of amitriptyline, the compound that “made” the antidepressant market. He was also involved in early assessments of Kuhn’s work on imipramine, Cade and others on lithium and tardive dyskinesia. He put together the first meeting on the history of the discovery of current treatments.
5 ALAN BROADHURST The Discovery of Antidepressants
After training in chemistry, Broadhurst joined Geigy Pharmaceuticals, at a time when pharmaceuticals were a small side-line for the company. He participated in the discovery of imipramine. He then retrained in psychiatry and entered clinical practice in time to see the transforming effect of the new drugs on that practice. He has seen the development of psychopharmacology from all sides.
6 SILVIO GARATTINI Independent Science in Psychopharmacology
Garattini was one of the first pharmacologists to work on the mechanisms of action of the new psychotropic drugs. Sensing the existence of a new frontier, he organised the first international psychopharmacology conference, an important first step in the creation of the framework within which psychopharmacology has developed. He then founded the Mario Negri Institute, an institute independent of both the Italian university system and the pharmaceutical industry. From this vantage point he has been an influential commentator on developments in psychopharmacology and medicine.
7 HEINZ LEHMANN Psychopharmacotherapy
Born in Germany, Lehmann emigrated to Montreal before the War. He was the first in North America to publish studies of the effects of chlorpromazine and later imipramine and was a key advocate for their subsequent use and the need to integrate drug treatment and psychological approaches to mental disorders. He became Professor of Psychiatry at McGill and Director of Psychopharmacology. He received many awards for his work, including in 1957 a Lasker Prize.
8 HANNS HIPPIUS The Discovery of Clozapine
Hippius became a psychiatrist in Germany, when psychopharmacology was being born. With colleagues he set up the AGNP, the German Society for Psychopharmacology. From early on he believed that antipsychotic activity could be produced without extrapyramidal side-effects and this belief led to the discovery of clozapine, the rediscovery of which in the 1980s was an important event. He was a founding member of the CINP.
9 HANNAH STEINBERG Experimental Psychology-Psychopharmacology
Steinberg, unusually for a psychologist in the 1950s, undertook postdoctoral research in pharmacology on the effects of nitrous oxide and other compounds with psychotropic effects. She then went on to study the effects of centrally acting compounds on animal behaviour. She was possibly the first to hold an officially designated university post in psychopharmacology.
10 JONATHAN COLE The Evaluation of Psychotropic Drugs
At the start of the psychopharmacological era, Cole became Director of the Psychopharmacology Research Centre, a branch of the NIMH, established on the back of funding donated by Congress for the evaluation of the new Psychotropic Drugs. His brief was to inaugurate the first multicentre clinical trials and to support a wide range of research across all the disciplines relevant to psychopharmacology. He subsequently moved into mainstream psychiatry taking a Chair in psychiatry at McLean where he put Prozac induced suicide on the map.
11 ALEC COPPEN Biological Psychiatry in Britain
Coppen was an early British ‘biological psychiatrist’. Early research on electrolytes in mood disorders was followed up with work in 5HT in mood disorders, leading to a Serotonin hypothesis of depression. Later research included studies on the role of plasma levels in the activity of antidepressant drugs, on the prophylactic effects of lithium in mood disorders and on the role of cortisol elevations in depression.
12 JULES ANGST The Myths of Psychopharmacology
Born in Zurich, Angst studied psychiatry with Bleuler and Jung. He was involved in early trials on a number of antidepressants, lithium and clozapine and played a significant role in developing methods to analyse the prophylactic effects of compounds like lithium. His subsequent work on the epidemiology of mental disorders led to the recognition of recurrent brief affective disorders. In other work he has challenged many of the myths of the field – such that antidepressants couldn’t be used to treat mania.
13 GEORGE BEAUMONT Clomipramine in Psychopharmacology
After training in medicine, Beaumont became the medical director of Geigy UK at a time when clomipramine was being developed. His strategies to ensure a market niche for this compound led to the virtual rediscovery of obsessive-compulsive disorders, which in twenty years have gone from being almost undiagnosed to being recognised as common and disabling. He also pulled together the first observations of the effects of psychotropics on sexual functioning, laying the basis for a new still unexplore area of psychopharmacology.
14 DONALD KLEIN The Discovery of Panic Disorder
Klein had an analytically oriented training in psychiatry in the 1950s. In the early 1960s, along with Max Fink at Hillside Hospital in New York, he became identified with early pharmacotherapy and conducted seminal studies on antidepressants and neuroleptics, in the course of which he noticed the phenomenon of panic attacks. Panic attacks have since become one of the most widely recognised psychiatric conditions. He was a key player in the framing of DSM-III.
15 HERMAN VAN PRAAG Psychiatry & The March of Folly
Herman van Praag qualified in psychiatry in Holland at the end of the 1950s. He began research in “biological psychiatry” at a time when this was tantamount to being thought of as being in league with the devil. His lectures were picketed, and he received death threats. He later worked for a decade as Head of Department at Einstein University in New York during the 1980s before returning to Holland. He has been one of the seminal thinkers within psychopharmacology.
16 MERTON SANDLER Chemical Pathology in Psychopharmacology
After training in medicine Merton Sandler specialised in chemical pathology and later in the origins and fate of neurochemicals implicated in the pathology of nervous disorders and in the mode of action of psychotropic compounds. Operating from a maternity hospital, he played a key part in both the ante-partum and post-partum development of British psychopharmacology and in the monoamine-oxidase story.
17 FLOYD BLOOM The Psychopharmacology of the Addictions
After studying medicine, Bloom went into psychophysiological research at NIMH and Yale. He subsequently became a Director of Neuroscience Research at the Salk Institute and later at The Scripps Research Institute. His primary research interest has been in the psychopharmacology of the addictions. He has written or edited several key texts which have brought psychopharmacology to a mass audience as well as some of the benchmark reference volumes and was an Editor of Science.
18 ALEXANDRA DELINI-STULA Psychotropic Drug Development from 1965-95
After qualifying, Alex Delini-Stula moved to a psychopharmacology career in the pharmaceutical industry, with Geigy, and then Ciba-Geigy and Roche. She has been associated with the development of maprotiline, the first SSRIs, the RIMAs and other psychotropic compounds. Her research has spanned the development of animal models, biochemical assays and clinical trial methodology.
19 GORDON CLARIDGE Individual Differences in Psychopharmacology
A psychologist, Claridge began his research with Hans Eysenck, at a time when Eysenck’s theories of personality and predictions as to the likely effects of psychotropic drugs made him one of the foremost pharmacopsychologists in the world. Claridge laid down many of the methodological principles which now guide work in this area. He also proposed a theory of schizophrenia as a nervous type – a forerunner of the modern schizotypy concept, which has had considerable influence.
20 MALCOLM LADER Psychopharmacology: Clinical and Social
Lader trained in psychiatry at the Institute of Psychiatry, where he became the first British clinician to hold the post of Professor of Clinical Psychopharmacology. His initial research was on the interface between psychophysiology and psychopharmacology. He became a leading authority on the nature and management of anxiety and he was prominent in debates on the use and abuses of the benzodiazepine minor tranquillisers.
21 HERBERT MELTZER A Career in Biological Psychiatry
Meltzer’s early career was paradigmatic of the careers in biological research in psychiatry in the US that developed following the introduction of the psychotropic drugs, working on biological markers in psychotic and mood disorders and clinical trial work on neuroleptics and antidepressants at NIMH and in Chicago. In the late 1980s, his career stepped out of the ordinary, when with John Kane and others he was involved in the rediscovery of clozapine and developed from this a series of hypotheses about antipsychotic mechanisms of action which were influential in subsequent drug development.
22 BRIAN LEONARD Behavioural Pharmacology in Drug Development
Trained in biochemistry and pharmacology in Birmingham when it was a nerve centre of British neuropsychopharmacology, Brian Leonard later worked in variety of university and industry settings. He was involved in the development of mianserin and has been a strong advocate of the use of animal models in psychopharmacology.
23 JOHN HUGHES The Discovery of the Opioid Peptides
After training in London with the Nobel-prize winner John Vane and subsequently at the NIMH, Hughes went to work with Hans Kosterlitz in Aberdeen. There he played the key role in the discovery of the enkephalins in the brain, one of the seminal discoveries in modern neuropharmacology. This work led to the award of a Lasker Prize. He has since moved into the pharmaceutical industry, becoming the Director of Parke-Davis Neuroscience Research Centre in Cambridge.
24 PETER WALDMEIER From Mental Illness to Neurodegeneration
After studying chemistry, Peter Waldmeier joined Ciba-Geigy when it was a world leader in psychotropic drug development. He was associated with the development of the SSRIs, the RIMAs and other psychotropic compounds. Few of these Ciba compounds reached the market – he tells the story of what went wrong. He later worked on neurodegenerative processes, when Ciba moved out of psychotropic drug development.
25 TOM BAN They Used to Call it Psychiatry
Born in Budapest, Tom Ban emigrated to Canada in 1956, where he completed his psychiatric training at the Verdun Hospital with Heinz Lehmann and the Allan Memorial Institute with Ewen Cameron. He became Director of Psychopharmacology at McGill University and later Professor of Psychiatry at Vanderbilt University. After retirement he moved to Toronto where he has established a multinational psychiatric corporation and a network for the study of the history of neuropsychopharmacology.
The PSYCHOPHARMACOLOGISTS – 2
1 THERESE LEMPERIERE In the Beginning in Paris
Lemperière began training psychiatry in Paris in 1949 before the discovery of chlorpromazine. She practiced and researched during the period when chlorpromazine, prochlorperazine, haloperidol and other neuroleptics were developed and psychopharmacotherapy took shape and was involved in the discovery of the anti-obsessive-compulsive action of clomipramine. She later became Professor of Psychiatry in Paris and after retirement was involved in the development of psychiatric services in Vietnam.
2 LEONARD COOK Pharmacology & Chlorpromazine
Cook did a PhD in pharmacology in Yale. He joined Smith-Kline & French and did the early laboratory experiments on chlorpromazine that persuaded the company to launch it as Thorazine. He established tests which discriminated between the effects of antipsychotics and minor tranquillisers and did early work on the effects of psychotropic agents on conditioned responses, drug discrimination and drug self-administration, many of the implications of which have not been followed up in clinical practice.
3 PAUL JANSSEN From Haloperidol To Risperidone
Janssen established his own pharmaceutical research company in Belgium in the early 1950s. Among the early compounds they created was haloperidol, which became the most widely used antipsychotic in the world. He charts the discovery of haloperidol, its trials and subsequent rise to a position of pre-eminence and work that has been done since on agents such as pipamperone and risperidone, as well as the changing face of drug development.
4 JOSEPH BRADY The Origins Of Behavioural Pharmacology
Brady qualified as an experimental psychologist in Chicago in the late 1940s. At the Walter Reed Hospital, along with Murray Sidman he established a behavioural pharmacology laboratory, where early work led to the discovery of the Conditioned Emotional Response, an animal paradigm sensitive to the effects of ECT and reserpine. This led to further work on psychotropic drugs and behavior and an involvement in harnessing the processes of psychotropic drug development to the study of behavior.
5 ROLAND KUHN The Discovery of Antidepressants
Kuhn was born in Switzerland in 1912. He trained in psychiatry with Jacob Klaesi and Ludwig Binswanger in a golden age in Swiss psychiatry. He moved to practice in Münsterlingen Hospital, where in the mid-1950s he was involved in the discovery of imipramine and later maprotiline and other antidepressants, agents which have done much to shape modern psychopharmacology. He is an outspoken critic of modern methods of evaluating psychotropic drug effects.
6 MAX LURIE The Enigma of Isoniazid
Lurie trained in psychiatry in Cincinnati, Chicago and Iowa and subsequently entered private practice in Cincinnati with his father, also a psychiatrist, in the years immediately after World War II. Along with Harry Salzer he investigated the effects of isoniazid in depressed patients before the discovery of antidepressants. Their work constitutes an unrecognised breakthrough in psychopharmacotherapy, the implications of which have still not been fully explored.
7 LOUIS LASAGNA Evaluation & Drug Development
Lasagna trained in medicine and pharmacology and helped establish the discipline of clinical pharmacology. He trained with Henry Beecher in Massachusetts General Hospital when the placebo, randomised control trials and the other techniques for evaluation of drug efficacy were being worked out. His work on evaluating the effects of analgesics paved the way for application of similar methods in psychopharmacology. He had a considerable role in shaping the 1962 FDA amendments on the question of evaluation.
8 LINFORD REES The Origin & Impact of RCTs in Psychiatry
Rees began training in psychiatry in Cardiff in the mid-1930s. He began a career in research which led to his involvement in the evaluation of early biological treatments in psychiatry from electronarcosis through to insulin coma, cortisone and chlorpromazine, conducting in the process some of the first controlled trials in psychiatry.
9 JOEL ELKES Psychopharmacology Receptors & Inner Pharmacy
Elkes was born in Lithuania, trained in medicine in London and then established a Department of Experimental Psychiatry in Birmingham in the early 1950s. There he and his wife Charmian conducted one of the first randomised controlled trials in psychiatry and with Philip Bradley outlined a vision of brain functioning in terms of neurotransmitters and receptors. He subsequently moved to the NIMH at St Elizabeth’s Hospital in Washington before becoming Professor of Psychiatry at Johns Hopkins University and established departments that recruited many of the subsequently leading figures in the field of psychopharmacology.
10 LEO HOLLISTER From Hypertension to Psychopharmacology
Working from a background in general medicine, Hollister ran some of the first controlled trials in psychiatry on reserpine and later chlorpromazine. He became a noted clinical trialist and ran large multi-centre trials looking at the effects of a variety of neuroleptics and antidepressants. He was the first to describe withdrawal syndromes to both benzodiazepines and antipsychotics. He later investigated the psychotomometic effects of hallucinogenic drugs and has been a leading figure in substance abuse.
11 MICHAEL SHEPHERD Psychopharmology: Specific & Non-Specific
Shepherd organised one of the first randomised control trials in psychiatry looking at the effects of reserpine in depression. He became a founder member of the CINP and Professor of Psychiatric Epidemiology at the Institute of Psychiatry from where he ran the MRC multicentre comparative trial of antidepressants which reported in 1965. He had important roles in establishing the methodology of treatment and in the development of psychiatric epidemiology, which led to the recognition of depression in primary care.
12 MOGENS SCHOU Lithium
Schou trained in psychiatry in Denmark, New York, and Norway before moving to Aarhus to work with Eric Strömgren where he became a Professor of Biological Psychiatry. Early in his career he ran a randomised control trial of Lithium in mania demonstrating its efficacy for that condition. He later outlined the prophylactic effects of lithium in recurrent affective disorders and his career is closely linked to lithium and methodologies for evaluating its usefulness, for which he has won Anna Monika and Lasker Prizes.
13 GEORGE SIMPSON The Emergence of Clinical Psychopharmacology
Simpson trained in psychiatry in McGill University with Ewen Cameron and then New York with Nathan Kline, where he participated in psychobiological research at Rockland State Hospital and witnessed the controversies surrounding the discovery of the psychotropic effects of iproniazid. He actively promoted the need for controlled assessment of both antidepressant and neuroleptic treatments and helped create The American Society for Clinical Psychopharmacology.
14 GERALD CURZON From Neurochemistry to Neuroscience
Curzon trained as a biochemist in Leeds and moved to the Institute of Neurology in London in the 1950s where he worked on the role of the serotonergic (5HT) system in psychiatric disorders and neurophysiological functions, such as feeding. His career illustrates how the individual brain disciplines come together in neuroscience and psychopharmacology. He is the archivist for the International Society of Neurochemistry and has an interest in applying quantitative methods to research on the history of psychopharmacology.
15 LESLIE IVERSEN Neuroscience and Drug Development
Iversen trained at Cambridge, the NIH and Harvard before taking up a position in the Medical Research Council Pharmacology Laboratories in Cambridge. He worked on reuptake mechanisms, the neurophysiology of GABA and excitatory neuropeptides and the role of the dopamine system in schizophrenia before becoming the Research Director of Merck, Sharp & Dome’s United Kingdom CNS research facility at Harlow, where he spent 10 years in the development of neuroprotective and other psychotropic agents, in particular modulators of neuropeptide systems, such as the Substance P and cholecystokinin systems.
16 JEFF WATKINS Excitatory Amino Acids
After graduating in chemistry from Perth and getting a PhD in Yale, Watkins moved to Canberra to work with the Nobellist John Eccles, where along with David Curtis he discovered the neurotransmitter properties of glutamate. It took 20 years before this work won acceptance and a further decade before it became mainstream. In the process, the NMDA receptor was discovered, offering the possibility of interventions that might be of benefit in neurodegenerative and a range of psychiatric conditions and treatment approaches that might target synaptic plasticity.
17 IRVING GOTTESMAN Predisposed to Predispositions
Gottesman trained in psychology on the Genetics of Behaviour in Minnesota with Paul Meehl in the 1950s. He researched psychiatric genetics with Eliot Slater in London in the 1960s, where early twin studies were seminal in re-establishing psychiatric genetics after World War II. This and subsequent studies in Minnesota and at Washington University have shaped the development of the field. He contributed to the Danish Genetic and High Risk Studies and as a consultant to Congress and other bodies on genetic research in mental illness and behaviour.
18 JUAN LOPEZ-IBOR The Psychopharmacology of Personality
Lopez-Ibor is from a family who have had several members play roles in both medicine and psychiatry in Spain. Early in his career he was involved in detecting the anti-obsessive effects of clomipramine. This led to an interest in notions of impulsivity and personality disorders and the role of serotonin. He has been involved in studies of gamblers and bullfighters.
19 OAKLEY RAY Psychology in American Neuropsychopharmacology
Ray trained in clinical psychology in the late 1950s before moving into experimental psychology. He later moved to Vanderbilt University as Professor of Psychology, Pharmacology and Psychiatry and became Chief of the Mental Health Service at a time when psychiatry in Nashville withdrew from service delivery. His interests lie in psychoneuroimmunology and his book Drugs, Society and Human Behavior is a best-seller. As Secretary of the American College of Neuropsychopharmacology he has involved ACNP in the history of psychopharmacology.
20 DAVID WHEATLEY The British Association for Psychopharmacology
As a General Practitioner in London in the 1950s, Wheatley formed a GP research group. This led to links with the Psychopharmacology Service Centre and subsequently ACNP. He was a prime mover in the establishment of the British Association for Psychopharmacology in 1974 – a foundation that crystallised many of the tensions of the field and had to involve their resolution. His career spans the development of trials from single investigator experiments to multi-centred, multinational trials.
21 IAN STOLERMAN Behavioural Pharmacology
Stolerman trained in psychology and pharmacology in London with Hannah Steinberg. This led to an interest in drug discrimination, drug self-administration and drug combinations. He later worked with Murray Jarvik in New York on the effects of nicotine on learning and memory. In London’s Institute of Psychiatry his work on substance dependence and drug discrimination has been influential. He was a co-founder of the European Behavioural Pharmacology Society.
22 PER BECH Measurement in Psychopharmacology
Bech began research with Ole Rafaelsen in Copenhagen on measurement in psychopathology and the development of rating scales for both depression and mania. He subsequently developed scales to measure aggression, social dysfunction and quality of life. He participated in the Cross-National Collaborative Studies on panic disorder. He stimulated the foundation of the European College of Neuropsychopharmacology.
23 MYRNA WEISSMAN Gerald Klerman & Psychopharmacotherapy
Weissman came to psychopharmacology from social work. With Gerald Klerman and Gene Paykel, she was involved in studies in Yale around 1970 that created interpersonal therapy and the development of instruments to measure social functioning. She participated with Klerman in the Cross-National Collaborative Studies of panic disorder and used both these and the Epidemiological Catchment Area Studies to establish psychiatric epidemiology. She gives an insight into Klerman’s role in the development of modern diagnostic systems, modern evaluative methods and the Osheroff case.
24 ISAAC MARKS Marketing the Evidence
Marks was a leading behaviour therapist. He is closely associated with the development of exposure therapy and an advocacy of its use for phobic and obsessive disorders. This led to his involvement in a series of influential studies in the 1970s and 80s comparing behaviour therapy and pharmacotherapeutic methods for OCD and subsequently Panic Disorder. These studies and the issues they raise are landmarks in the field.
25 VAGN PEDERSEN & KLAUS BOGESO Drug Hunting
Pedersen and Bøgesø joined the Lundbeck around 1970, Pedersen in market development and Bøgesø in medicinal chemistry. They give a perspective of the origins of Lundbeck, the role of PV Pedersen in establishing CNS research with antipsychotics like chlorprothixene and flupenthixol and antidepressants like amitriptyline and nortriptyline. They outline the evolution of depot and acuphase antipsychotics as well as the development of citalopram and sertindole, the recent specialisation of the company in CNS research and development and the turn to combinatorial chemistry in drug development programmes.
26 ROGER PINDER Psychopharmacology: Approaching Rationality?
Pinder trained in medicinal chemistry with Alfred Burger in the University of Virginia. He then worked at the UK Chemical Defence Establishment in Porton Down on hallucinogens before moving to Holland as Scientific Director for CNS Drugs at Organon Pharmaceuticals. There he participated in the development of both mianserin and mirtazapine and was centrally involved in managing the regulatory difficulties that befell both mianserin in the 1980s and the third generation oral contraceptives since, difficulties which illustrate the nature of risk-benefit assessments in pharmaceutical developments.
27 PAUL LEBER Managing Uncertainty
28 PAUL LEBER Regulating Medicines.
After training in medicine and pathology, Leber subsequently changed career and entered psychiatry at a time of upheaval when the new classificatory system – DSM III – was being developed. He joined the Food and Drug Administration where he became head of the CNS section. While there, he was responsible for a renewed emphasis on the importance of a placebo arm in clinical trials, a change of emphasis that had a major impact on drug development. He outlines the realisation of the importance of this as well as the impact of AIDS on the approval process.
The PSYCHOPHARMACOLOGISTS – 3
1 COMMITE LYONNAIS (CLRTP) Exploring a New World.
This unique group formed in 1956, comprised pharmacologists, asylum and university psychiatrists. It included committed pharmacotherapists and anti-psychiatrists, giving the observations made by the group a particular importance. Formed by Paul Brouillot of Rhône-Poulenc it managed to negotiate a balance between scientific and commercial needs. A startling number of discoveries emerged from their work, including the recognition of the anti-obsessive effects of imipramine by Jean Guyotat, the discovery of valpromide by Pierre Lambert, the discovery of the “incisive” neuroleptics by Paul Broussole, and the antidepressant trimipramine. The interview involves Pierre Lambert, Jean Guyotat, Paul Broussolle, Paul Brouillot, Patrick Lemoine and Jacques Greffe with questions from Isabelle Soares-Bouchaud and David Healy.
2 OLDRICH VINAR A Psychopharmacology That Nearly Was.
Vinar was an early contributor to European psychopharmacology, who had the benefit and handicap of being isolated from the development of Western psychopharmacology. Eastern European clinicians were forced to come up with different evaluative methods and developed concepts free from pharmaceutical company market development influences. This held certain kinds of development back but also fostered others. Vinar was a Professor of Psychiatry and one of the key movers in Czech psychopharmacology.
3 JOSEF KNOLL The Psychopharmacology of Life & Death.
Knoll studied pharmacology in Budapest before the Hungarian revolution, and later became Professor of Pharmacology in one of Europe’s oldest departments. He tells a dramatic story about how ideology and politics influenced conceptual developments. And an even more dramatic story about the discovery of a unique drug, deprenyl, underlying which is a possible vision of alternate mechanisms of drug action. The deprenyl story sheds an ironic light on the ideologies and politics that shape Western drug development, and also bridges the divide between enhancement technologies and disease concepts.
4 JOSEPH SCHILDKRAUT The Catecholamine Hypothesis.
Schildkraut’s Catecholamine Hypothesis defined the psychopharmacological era. One may quibble with its details but the paper was foundational – the 1960’s equivalent to Freud’s The Interpretation of Dreams. The circumstances in which it was written, the controversies it generated as well as the subsequent research program it gave rise to are hugely important. In fact, efforts to test the hypothesis gave rise to the research, which led on to DSM III and through that to a transformation of psychiatry. Despite this Schildkraut was one of the foremost advocates of a psychotherapeutic input to mental health care.
5 ALEC JENNER Catatonia, Pink Spots & Antipsychiatry.
Trained with Erwin Stengel, Jenner emerged as a leader in early European biological psychiatry, later becoming the Professor of Psychiatry at Sheffield. He was the first to test a benzodiazepine in a controlled trial, while participating in biological research at a time when it seemed the major psychiatric syndromes might successively be reclassified as metabolic disorders. His research involved debunking the pink spot theories of schizophrenia. At the same time, antipsychiatry was growing as an intellectual and political force and Jenner was a close friend of Ronnie Laing. These different perspectives have forced him to become unusually philosophical about psychiatry and psychopharmacology.
6 DICK BARLOW Receptors & Chemists
Since Paul Ehrlich’s work with methylene blue which led to the concept of a Magic Bullet, the receptor has been the dominant metaphor in 20th century therapeutics. Vigorous battles were fought between chemical pharmacologists, who could not conceive of how drugs could act other than on receptors, and physiologists, for whom physiological processes had primacy. Barlow had a ringside seat at this fight working as he did in the Edinburgh department of pharmacology where Clark first formulated modern receptor theory and Gaddum discovered two serotonin receptor subtypes, as pharmacologists gained the upper hand.
7 ROBERT STEPHENSON Receptors & Classical Pharmacology
Stephenson worked alongside Barlow in Edinburgh. He was a theoretician who recast receptor theory, transforming it in ways that therapeutics has still not caught up with. Building on contributions from Clark, Schild, Burns, Gaddum and Patton, Stephenson’s work represents a golden age of British pharmacology before molecular and high technology developments led to the visualisation of receptors and the passing of the baton for innovation elsewhere.
8 GEORGE ASHCROFT The Receptor Enters Psychiatry (1)
Ashcroft was an original biological psychiatrist as this species emerged in the late 1950s. His research led to the earliest serotonin hypothesis of mood disorders. He also introduced the first receptor hypothesis into psychiatry months before the technical developments that led to the demonstrations that receptors actually exist. Later as Professor of Psychiatry in Aberdeen he was involved with the earliest magnetic resonance imaging research.
9 DONALD ECCLESTON The Receptor Enters Psychiatry (2)
Eccleston joined Ashcroft in Edinburgh, where they explored the functioning of the serotonin system in depression, laying the groundwork for the later development of drugs like Prozac but also for what was to become in other hands something of a biomythology about serotonin levels in depression. This work gave rise to combination therapies in depression, including lithium augmentation strategies, aimed at manipulating receptor functioning. But neither Eccleston or Ashcroft were hostile to psychotherapeutic or other interventions. Eccleston later became Chairman of the Department of Psychiatry at Newcastle.
10 SOLOMON SYNDER Visualising Receptors & Beyond.
Snyder was seen as one of the most accomplished neuroscientists of his generation with a string of breakthroughs leading to Lasker Prizes and other awards. He contributed to the receptor story by discovering the opiate receptor and later the radiolabelling serotonin receptors, which confirmed the original insights of pharmacologists. Snyder’s subsequent work, though, including the discovery of the neurotransmitter functions of Nitric Oxide and other “strange” chemicals in the brain, subverts the classic receptor story, making the brain seem in many ways more mysterious than is commonly portrayed.
11 FRIDOLIN SULSER From the Presynaptic Neurone to the Receptor
Having trained with some of the giants of classic physiology and pharmacology, Hess and Brodie, Sulser became Professor of Pharmacology at Vanderbilt University and one of the magisterial figures of psychopharmacology in the late 20th century. His work brought receptors into the antidepressant story with the Beta-adrenergic downregulation hypothesis. This was at the time one of the key developments in biological psychiatry, both in terms of drug development but also in terms of capturing the imaginations of psychiatrists and pharmacologists and creating a new language for psychiatry.
12 TERUO OKUMA The Psychotropic Effects of Carbamazepine
The idea that all the discoveries in psychopharmacology were made in the 1950s is wrong. The mood stabilising effects of valpromide and carbamazepine came later. These were arguably more subtle discoveries and accordingly harder to make. Their effects have taken longer to impact on psychiatry but are doing so increasingly in the 1990s leading to use of anticonvulsants as mood-stabilizers. Okuma, Professor of Psychiatry in Tokyo, discovered the psychotropic effects of carbamazepine, and brings out this story.
13 TOSHI-HIRO KOBAYAKAWA Psychopharmaceuticals in Japan
The Japanese psychopharmacology market has been second only in size to the American marketplace. It is remained and anxiolytic sector when Westerners became depressed. The reasons for this and the role of Japanese companies in ongoing global research are laid out by Kobayakawa who joined Yoshitomi Pharmaceuticals from university just at the time the psychotropic drugs began to come on stream.
14 MICHIO TORU Neurotransmitter Research in Japan
Schizophrenia research in Japan has been of more than ordinary interest. When the students revolted in the late 1960s worldwide, in Japan the protests lasted 10 years and the department of psychiatry was occupied. Their concerns related to biological research in schizophrenia, of which Toru was a leader in the 25 years since the student protests. The concern with psychiatry expressed in the revolutions of 68, which transcended global cultural differences, stands in strange contrast to the neglect of Japanese discoveries by the West. Toru outlines a number of these from amphetamine induced psychosis, to the treatment of delirium with mianserin and Japanese roles in neurotransmitter research.
15 RACHEL KLEIN Childhood Psychopharmacology
Where once the major ideological battles in psychiatry focused on the schizophrenogenic mother, hyperactivity and the use of pharmacotherapy has become the focus of competing forces. Klein trained as a psychologist and accordingly might have been expected to be on the other side of the therapy wars, but she has been one of the key figures in the developing methods to assess the effects of drugs on childhood syndromes.
16 JUDITH RAPOPORT Psychopharmacotherapy & Child Psychiatry
One of the most dramatic stories in psychopharmacology has been the discovery of the benefits of clomipramine for OCD. Rapoport’s studies in children with OCD challenged traditional models of the place of pharmacotherapy for this group of conditions formerly termed neurotic and understandings of the nature of this condition. Her ongoing work as Head of the Child Pychiatry branch of the NIMH on juvenile psychoses continues to break new ground. Her cultural impact, through works like The Boy Who Couldn’t Stop Washing, has been almost as great as her scientific work.
17 ROBERT DOMENJOZ From DDT to Imipramine
Domenjoz was the product of a classical European training in pharmacology. He joined Geigy and was the discoverer/creator of more original drugs than any other pharmacologist, including DDT, phenylbutazone and later imipramine. He gives a picture of the European pharmaceutical companies from which the central discoveries of the psychopharmacological era came.
18 RAYMOND BATTEGAY Swiss Psychiatry & Psychopharmacology
In the early days of psychopharmacology, nowhere was more important than Basel, which under John-Eugen Staehelin was among the first centres to embrace chlorpromazine. The contributions of Steck, Labhardt and Staehelin to concepts of neuroleptic action were decisive. Those of Kielholz and Battegay were similarly influential when it came to antidepressant psychopharmacotherapy. Battegay describes the contributions of these various figures linked to the Basel Department of Psychiatry.
19 SAMUEL GUZE The Neo-Kraepelinian Revolution
Over-simplistic though it be, St Louis is commonly portrayed as the one department within the US that held out against the Freudian tide, from where in the fullness of time the Neo-Kraepelinian counter-revolution was borne. Its key figures were Eli Robins and Sam Guze. Their chosen weapon operational criteria. Guze, the Chairman of Psychiatry at St Louis during this period, outlines his reluctant conversion into a psychiatrist, the development of his partnership with Robins and the triumph of some of their ideas in DSM-III.
20 ROBERT SPITZER A Manual for Diagnosis & Statistics
As a junior researcher in NYS Psychiatric Institute, Spitzer got involved as a consultant to the American Psychiatric Association’s Taskforce on nomenclature and statistics that developed the 2nd Edition of the Diagnostic and Statistics Manual and later in the debate about the medical status of homosexuality. This background propelled him to Chairmanship of the 3rd Edition of the DSM process, which revolutionized world psychiatry.
21 MAX FINK Neglected Disciplines in Psychopharmacology
If the receptor is the key metaphor of 20th century psychopharmacology, the fortunes of EEG techniques are its counterpoint. These investigations of behaviour at a molar rather than a molecular level declined with the rise of receptor technologies. This story is beautifully outlined by the leading protagonist of pharmaco-EEG, Max Fink who started his career in Hillside Hospital. Fink subsequently became involved in the successful campaign to save ECT, which was a dramatic struggle for the soul of psychiatry. On the way he stumbled onto catatonia and along with co-workers helped to resurrect this syndrome.
22 IAN OSWALD The Hypnotic Business
Oswald was another exponent of EEG techniques, who became one of the leading figures in the assessment of hypnotics and a leading psychopharmacologist in the 1960s and 1970s. A Professor of Psychiatry in Edinburgh, his work on hypnotics ultimately embroiled him in what was then the longest libel trial in English legal history. This interview indicates how it might be necessary for future historians to consult lawyers if they want to find out what really happened in the psychopharmacological era.
23 DAVID SHEEHAN Angles on Panic
The emergence of panic disorder in DSM-III and its subsequent development into a widely recognized disorder at street level is one of the most astonishing stories in contemporary psychopharmacology. Sheehan was working in Boston when the story began and gives an account of this development, outlining how neo-Kraepelinism impacted on 1990s psychopharmacology. He also covers the emergence of the use of anticonvulsants for a range of conditions that have hitherto been seen as personality disorders.
24 EDWARD WARAWA From Neuroleptics to Antipsychotics
Warawa trained in medicinal chemistry, with Aldrich and later Abbott, on anticholinergic and other agents, among which was the precursor of the first neurokinin receptor antagonist. He joined ICI, later Zeneca and Astra-Zeneca as a CNS pharmacologist, at the opening of the Wilmington site, now the headquarters for CNS research and development. His brief was to develop an antipsychotic. He outlines the possible strategies available in the mid-1970s and the many avenues followed before the successful discovery of Seroquel in the mid-1980s.
25 PIERRE SIMON Twenty-First Century Drug Development
Simon trained in pharmacology with Jean-Francois Boissier and in psychiatry with Pierre Deniker, giving him an insider’s perspective on the French psychopharmacology scene. He was uniquely qualified in psychopharmacology and from this base played a major part in channelling European thinking about further drug development. This eventually led to his joining Sanofi pharmaceuticals, where he describes his efforts to re-orient development from a 1970s style toward what will be needed in the 21st century.
26 JEAN THUILLIER Ten Years That Changed Psychiatry
Thuillier worked in Jean Delay’s Department of Psychiatry when chlorpromazine was discovered and witnessed at first hand the contributions of Laborit, Delay and Deniker, the difference the discovery of chlorpromazine made and the reasons why this seminal discovery was never recognized in the way that might have been expected. He presented the first doctoral thesis on psychopharmacology and subsequently became a senior figure in both pharmacology and psychiatry. He headed the first INSERM psychopharmacology unit, found his own drug company, discovered a psychotropic drug and since retirement has authored prize-winning works in both fiction and on the history of psychiatry.
The PSYCHOPHARMACOLOGISTS 4
1 BARNEY CARROLL The Dexamethasone Suppression Test
Carroll, an Australian, became a prominent American psychiatrist. He created the Dexamethasone Suppression Test (DST), a test for diagnosing melancholia, which stands in marked contrast to the operational approach to diagnosis adopted by DSM III. This is covered in a first interview. He also became a key figure in what ended up becoming the Sunshine Act – an effort to make transparent the links between physicians and the pharmaceutical industry. A second interview covers this story.
2 BARNEY CARROLL Conflicts of Interest
3 DEREK RICHTER Early Days in Neuroscience
Richter was one of the first neuroscientists. His account tells of the difficulties neurochemists had in being taken seriously by physiologists and the rudimentary state of the field early on – interrupted by a World War. A world before scientific journals and before the operation of corporations like Pergamon and Elsevier
4 ROSS BALDESSARINI Neuroscience and Clinical Practice
Having trained at Hopkins and the NIMH, Baldessarini moved to Boston in time to see a changing for the guard from psychoanalysis to psychopharmacology. He became an important player in early research on dopamine in schizophrenia and in tardive dyskinesia. He offers a skeptical overview of the fads and fashions of American psychiatry, and our prospects for the future
5 MANDEL COHEN Operational Criteria
When the creators of DSM III talk about how things were before 1980, talk invariably turns to Cohen who had adopted the idea of operational criteria before anyone else. He was almost the only biological psychiatrist left standing in Boston in the heyday of psychoanalysis but outside of Boston, he was and remains largely unknown in American and world psychiatry.
6 RONNIE SANDISON Psychedelic Therapy in the 1950s
Sandison was a British psychiatrist who pioneered LSD therapy during the 1950s and 1960s. LSD was pressed into use for a range of problems from dyspareunia to homosexuality, which sound problematic now, but it also increased awareness of prior childhood trauma and was helpful in substance abuse problems.
7 LESTER GRINSPOON Marijuana, Ecstasy and Related Drugs
Based in Boston, Grinspoon perhaps did more than anyone else to give marijuana, ecstasy and other psychedelic drugs a respectable place in therapy. His work seems to be coming to fruition soon after his death.
8 ALEXANDER SHULGIN Psychedelics outside the Box
Based in the San Francisco area, Shulgin was a chemist who worked initially with the Dow Chemical company and later as a freelance researcher at a time when research was rapidly becoming increasingly constrained and bureaucratised, choking off psychedelic research. In this period, he developed an interest in psychedelic drugs and convened groups of other interested souls to help map the effects of tryptamines and phenylethylamines on mental states that is cataloged in Tihkal and Pihkal.
9 ALEXANDER SHULGIN Psychedelics Again
A second interview by Claus Langmaack
10 ARNOLD MANDELL From Antidepressants to Psychedelics
Coming from a conventional background, Mandell rose to become head of department in San Diego at a time when research in pyschopharmacology was becoming increasingly constrained the possibilities of marrying psychopharmacology and psychodynamics was shrinking rapidly – Listening to Prozac was being replaced by Let Them Eat Prozac.
11 CHARLES NEMEROFF From Icthyology to Psychopharmacology
Nemeroff came into psychopharmacology when the field of biomarkers and neuroendocrinology was already established. He became a leading Key Opinion Leader.
12 LEON EISENBERG Stimulants and Children
Eisenberg commands respect across social, biological and psychological camps in mental health. He was the Professor of Psychiatry in the Department of Social Medicine in Harvard Medical School and a notable social psychiatrist but was also the first person to show by controlled trial methods that methylphenidate worked for what was later recognised as ADHD. This syndrome has been the focus of ideological division in recent years and a target for critics of pharmacotherapy. There also appear to be wildly different prevalence rates for the disorder between the US and Europe. As the one of the creators of the syndrome, Eisenberg is uniquely placed to comment.
13 KAREN BARTH MENZIES Pursuing the Black Box
Barth, as she was, trained as a lawyer with Andy Vickery in Houston and Baum Hedlund in Los Angeles. Baum Hedlund were involved in early Prozac suicide cases and kept the flame burning when other law firms dropped out. Along with Cindy Hall, she took their concerns to Senators like Chuck Grassley and ultimately their campaigning led to a Black Box Warning on antidepressants for children and later were incorporated in the Sunshine Act.
14 SKIP MURGATROYD Conversations with Corporations
Murgatroyd drove taxis until the age of 40 when he took up law, then helped found a law firm which made him a wealthy man and able to retire. In retirement, he took an interest in the problems of the SSRI group of drugs and how pharmaceutical corporations had managed to hide the obvious damages these drugs can cause – perhaps getting them to reveal more than they intended in the course of conversations with them.
15 CHARLES MEDAWAR Bidet view of Psychopharmacology
Medawar is the closest Britain has had to a Sidney Wolfe or Ralph Nader. He did more than anyone else to put benzodiazepine and later SSRI dependence on the map, efforts that others took credit for. His vision though was broader than psychotropic drugs and Britain. He was a pillar of Health Action International and was the first to crystallise the notion of Pharmageddon – that we might simultaneously end up having too many drugs and too few.
16 BARBARA MINTZES International Drug Policy and Women’s Issues
An American living in Canada, Mintzes entered the world of health activism through a focus on women’s issues and the effects of Diethylstilbestrol – DES – on both women and men. She joined Health Action International and became a key figure in the struggle to avoid an extension of the practice of Direct-to-Consumer-Advertising of pharmaceuticals beyond the United States.
17 NANCY OLIVIERI
When she attempted to grapple with the side effect of a new treatment for thalassemia that she had pioneered, Olivieri ran foul of Apotex and more surprisingly the University of Toronto. Her story stands out as perhaps the clearest symbol of what can happen to a clinician who falls foul of a pharmaceutical company – a story that continues to throw up twists twenty years ago it first began.
18 PETER GOETZSCHE Cochrane Collaboration
Goetzsche began work in the pharmaceutical industry before switching back to medicine and ultimately becoming a founding member of what came to be called the Cochrane Collaboration, a key institution within the Evidence Based Medicine movement. In 2019 however Cochrane was split apart when Goetzsche was expelled from the organisation most likely in part for calling the organisation out for tolerating a sequestration of clinical trial data.
19 DAVID CLARK Community Care
The ideas of community psychiatry and therapeutic communities that are linked to the 1950s and may have seemed facilitated by the new psychotropic drugs then emerging in fact had their origin in pioneers like David Clark and Maxwell Jones who were shaped by their experience of the War.
20 ALAN RILEY Drugs and Sex
Riley was a British physician who focused on sexual effects of medications, primarily with a view to treating dysfunction. He convened symposia, wrote books and lectured on a topic that was ignored by the mainstream.
21 LEONORE TIEFER Drugs and Sexual Relationships
When the pharmaceutical industry hoped to make a killing in the world of female sexual dysfunction in the wake of their success with Viagra, they came up against Leonore Tiefer who with colleagues organized a New View of female sexuality and successfully blocked the licensing of a series of drugs aimed at women and their sexual difficulties
22 DAVID HORROBIN Leaving Psychopharmacology
Horrobin’s career was unique. By a circuitous series of events, he became interested in prolactin and then psychotropic drugs and prostaglandins and psychotropic drugs as probes for endocrine systems. This led to observations that benzodiazepines could trigger cancers and his sacking from McGill university. As a result he set up his own company, Scotia Pharmaceuticals to investigate the role of fatty acids on the prostaglandin system and possible benefits in medical disorders. Horrobin unfortunately died young.
The Shipwreck of the Singular
By Dr. David Healy
Publisher: Samizdat Health Writer’s Co-operatrive Inc.
Publish Date: Forthcoming in 2021