The Psychopharmacological Revolution in the USSR: Schizophrenia Treatment and the Thaw in Soviet Psychiatry, 1954-64.

Twentieth-century psychiatry was transformed in the 1950s and 1960s by the introduction of powerful psychopharmaceuticals, particularly Chlorpromazine (Thorazine). This paper examines the reception of Chlorpromazine in the Soviet Union and its effect on the Soviet practice of psychiatry. The drug, known in the USSR by the name Aminazine, was first used in Moscow in 1954 and was officially approved in 1955. I argue that Soviet psychiatrists initially embraced it because Aminazine enabled them to successfully challenge the Stalin-era dogma in their field (Ivan Pavlov's 'theory of higher nervous activity'). Unlike in the West, however, the new psychopharmaceuticals did not lead to deinstitutionalisation. I argue that the new drugs did not disrupt the existing Soviet system because, unlike the system in the West, the Soviets were already dedicated, at least in theory, to a model which paired psychiatric hospitals with community-based 'neuropsychiatric dispensaries.' Chlorpromazine gave this system a new lease on life, encouraging Soviet psychiatrists to more rapidly move patients from in-patient treatment to 'supporting' treatment in the community.

Henri Laborit and the inhibition of action.

Henri Laborit was one of the founders of modern neuropsychopharmacology, having discovered, or participated in, the discovery of chlorpromazine, gamma-OH, clomethiazole, and minaprine. He also put forward a theory regarding the necessity of counteracting the negative consequences of defense mechanisms during anesthesia or behavioral inhibition. The scope of his work covers neurophysiology, pharmacology, psychiatry, and psychosomatics. His independence of spirit meant that most of his research was not done within university settings.

Henri Laborit fue uno de los fundadores de la moderna neuropsicofarmacología al descubrir o participar en el descubrimiento de la clorpromazina, el gama-hídroxíbutirato, el clometiazol y la minaprina. Él también adelantó una teoría relacionada con la necesidad de contrarrestar las consecuencias negativas de los mecanismos de defensa durante la anestesia o inhibición conductual. El alcance de su trabajo se extiende a la neurofísiología, la farmacología, la psiquíatría y la psicosomática. Su independencia de espíritu se tradujo en que la mayor parte de su investigación la realizó fuera de los ambíentes universitarios.

Henri Laborit fut l'un des pères fondateurs de la neuropsychopharmacologie moderne. Il a découvert, ou participé à la découverte de molécules telles que la chlorpromazine, le gamma-OH, le clomethiazole, et la minaprine. Il est également à l'origine d'une théorie sur la nécessité de neutraliser les effets négatifs des mécanismes de défense pendant l'anesthésie ou l'inhibition comportementale. Ses travaux ont porté sur des domaines aussi variés que la neurophysiologie, la pharmacologie, la psychiatrie et la psychosomatique. Jaloux de son indépendance, il a effectué la plupart de ses recherches hors du cadre universitaire.

[The praise of the leak: a tribute to Henri Laborit (1914-1995)]. / L'éloge de la fuite:hommmage à Henri Laborit (1914-1995)

Henri Laborit (1914-1995) was a French military MD. He contributed to the discovery of an important molecule that has changed the face of psychiatry, namely chlorpromazine, which became the first drug in the class of first-generation antipsychotics, which later led to the dopamine hypothesis of schizophrenia. He did not receive the Nobel Prize for this discovery, unlike Daniel Bovet who get the Nobel Prize for the discovery of antihistaminics. Henri Laborit is also the author of a book that has contributed to the popularization of neurosciences in France, "The Praise of flight" (1976).

[Drug treatments, from chlorpromazine to new molecules]. / Traitements médicamenteux, de la chlorpromazine aux nouvelles molécules.

The history of drug treatments, and particularly the discovery of certain molecules, led toan evolution in psychiatric practices. The discovery of the therapeutic properties of chlorpromazine in 1952 by Jean Delay and Pierre Deniker revolutionised the relational process between patients and caregivers.The perspectives are encouraging, notably in the areas of schizophrenia and mood disorders.

The chlorpromazine enigma.

Two revolutionary drugs were introduced into psychiatry in the early 1950s for the treatment of agitated mental patients - reserpine and chlorpromazine. These drugs initiated the modern era of drug treatment for schizophrenia and other psychoses. Early research revealed that, although the pharmacological profiles of the two drugs overlapped considerably, they had different mechanisms of action. The mechanism of action of reserpine was determined first: it depletes monoamines from the brain and other tissues. By contrast, chlorpromazine has little or no effect on brain monoamine concentrations. The mystery created by two drugs that have similar pharmacological profiles but different mechanisms of action is the chlorpromazine enigma. For about eight years after the mechanism of action of reserpine was determined, researchers followed several false leads about the mechanism of action of chlorpromazine. Then, in 1963, Arvid Carlsson and Margit Lindqvist proposed that chlorpromazine (and haloperidol) work by blocking "monoaminergic" receptors. It was quickly determined that dopamine receptor blockade was the most important action. Although the idea of chemical communication between central neurons had yet to gain wide acceptance, this idea was central to resolving the chlorpromazine enigma.

Another view of the history of antipsychotic drug discovery and development.

Chlorpromazine initiated effective pharmacotherapy for schizophrenia 60 years ago. This discovery initiated or stimulated key developments in the field of psychiatry. Nonetheless, advances in pharmacotherapy of schizophrenia have been modest. Psychosis remains the primary aspect of psychopathology addressed, and core pathologies such as cognition and negative symptom remain unmet therapeutic challenges. New clinical and basic neuroscience paradigms may guide the near future and provide a more heuristic construct for novel and innovative discovery.

The introduction of chlorpromazine in Belgium and the Netherlands (1951-1968); tango between old and new treatment features.

The introduction of chlorpromazine in Belgium and the Netherlands demonstrates an intriguing tango between old and new treatments. Chlorpromazine, marketed by the French company Rhône Poulenc entered psychiatry as an adjunct to existing therapies. Instead of promoting chlorpromazine as a revolutionary therapy, we see early efforts to market Largactil as a supplement to the armoury of psychiatric treatments. These marketing efforts matched the idiosyncrasies of national and local styles and cultures. Despite continuities with earlier therapeutic developments, we support the notion of a therapeutic revolution. In the early sixties supply and demand provoked a turn towards more standardized therapeutic regimes.

Terra incognita: an historiographic approach to the first chlorpromazine trials using patient records of the Psychiatric University Clinic in Heidelberg.

Psychiatrists have often referred to the discovery of new psychopharmaceutical drugs in the 1950s as a 'therapeutic revolution', which allowed physicians to observe und measure therapeutic effectiveness easily. Contrary to this view, this article will argue that psychiatrists needed the patient's subjective voice to evaluate the effects of the drugs. In a micro-analysis of hospital records of the first patient to be treated with chlorpromazine in the Heidelberg clinic in 1953, I show the different perspectives of doctors and patients on the diagnosis and treatment.The analysis points up how difficult it was to get an impression of the drug's effectiveness.The article emphasizes the importance of the new perspective that includes the patient's voice in the history of psychotropic drugs after 1945.

[A difficult stabilisation. Chlorpromazine in the fifties in Belgium]. / Une stabilisation difficile. La chlorpromazine dans les années 1950 en Belgique.

Through a Belgian case study the article tries to trace the gradual stabilisation of chlorpromazine as an antipsychotic in the 1950s. By varying ranges and angles of approach it shows the heterogeneity of actors involved and the semantic bricolage that accompany the marketing of the first antipsychotic. Far from being a revolution, the presence of Largactil in psychiatric practice is rather characterised by integration into a wider range of medicines and sinuous searching to give sense to this new drug.

Neurosyphilis, malaria, and the discovery of antipsychotic agents.

Four of the most disabling human diseases are syphilis, malaria, schizophrenia, and manic-depressive illness. The history of the development of treatments for these seemingly unrelated disorders intersects at several points. Treatment of tertiary cerebral syphilis (general paresis) by inducing fever with malaria led to a Nobel Prize. Although attempts to synthesize quinine, a plant product effective against malaria, failed, these efforts encouraged industrial organic chemists to synthesize many useful substances, including dyes, antibiotics, and antihistamines. The aniline-derived dye methylene blue was a member of a new class of polycyclic chemicals, the phenothiazines. Efforts to modify phenothiazines to find an antimalarial agent also failed but led to novel antiemetic-sedative antihistamines, including promethazine, promazine, and eventually chlorpromazine--the first effective treatment for schizophrenia and mania. Chlorpromazine has antipsychotic and antimanic properties, and it revolutionized the therapeutics of psychotic illnesses.

[Fritz Flügel (1897-1973). Early research on neuroleptics]. / Fritz Flügel (1897-1973). Frühe Forschungen auf dem Gebiet der Neuroleptika.

In the early 1950s, Fritz Flügel and his colleagues at the Neurology Clinic of the University of Erlangen in Germany contributed greatly to the clinical introduction of chlorpromazine in German psychiatry. Flügel's clinical work made possible in exemplary fashion the first German psychiatric research on neuroleptics. Between 1953 and 1963, scientists were trying to find a theoretical explanation for the positive psychic effect which had become evident during empirical tests with the new substance. Within a few years, the new drug had its breakthrough, which simply was based on worldwide therapeutical success and good empirical results. That already had happened about 10 years before Carlsson came up with the first plausible theory of neuroleptic function by formulating the dopamine hypothesis in 1963. This brought new energy and developments in psychiatric research in general. Newly developed theses have thoroughly changed the therapeutic approach in psychiatry and the way in which pathophysiological contexts of the brain are understood.