A History of the Pharmacological Treatment of Bipolar Disorder.

In this paper, the authors review the history of the pharmacological treatment of bipolar disorder, from the first nonspecific sedative agents introduced in the 19th and early 20th century, such as solanaceae alkaloids, bromides and barbiturates, to John Cade's experiments with lithium and the beginning of the so-called "Psychopharmacological Revolution" in the 1950s. We also describe the clinical studies and development processes, enabling the therapeutic introduction of pharmacological agents currently available for the treatment of bipolar disorder in its different phases and manifestations. Those drugs include lithium salts, valproic acid, carbamazepine, new antiepileptic drugs, basically lamotrigine and atypical antipsychotic agents (olanzapine, risperidone, quetiapine, ziprasidone, aripiprazole, asenapine, cariprazine and lurasidone). Finally, the socio-sanitary implications derived from the clinical introduction of these drugs are also discussed.

Magic bullets for mental disorders: the emergence of the concept of an "antipsychotic" drug.

When "antipsychotic" drugs were introduced into psychiatry in the 1950s, they were thought to work by inducing a state of neurological suppression, which reduced behavioral disturbance as well as psychotic symptoms. This view was reflected in the name "neuroleptic." Within a few years, however, the idea that the drugs were a disease-specific treatment for schizophrenia or psychosis, and that they worked by modifying the underlying pathology of the condition, replaced this earlier view, and they became known as "antipsychotics." This transformation of views about the drugs' mode of action occurred with little debate or empirical evaluation in the psychiatric literature and obscured earlier evidence about the nature of these drugs. Drug advertisements in the British Journal of Psychiatry reflect the same changes, although the nondisease-specific view persisted for longer. It is suggested that professional interests rather than scientific merit facilitated the rise of the disease-specific view of drug action. The increasing popularity of atypical antipsychotics makes it important to examine the origins of the assumptions on which modern drug treatment is based.

East-Side story: the standardisation of psychotropic drugs at the Charité Psychiatric Clinic, 1955-1970.

The present article illustrates the history of psychotropic drugs introduced in the German Democratic Republic (GDR) from 1945 onwards. We begin by examining the introduction of an anti-depressant and a tranquilizer at the university psychiatric clinic, Charité, in East Berlin. On the basis of patient files, we consider the monitoring routines, altered by the use of psychotropic drugs, and the difficulties that arose when these routines were translated into existing research programs. In the 1960s, attempts to evaluate the psychiatric practice were based on psychopathology whereas at the end of the 1960s there was a shift to "target symptoms".

Meprobamate-tranquilizer or anxiolytic? A historical perspective.

Meprobamate was the first successful anti-anxiety drug of the modern era. On the 50th anniversary of its introduction, the authors trace the development of its synthesis, marketing and runaway success to understand the scientific and socio-political factors that may have shaped its use in clinical psychiatry. The relationship of this drug to the earlier development of chlorpromazine is explored to clarify the imperatives of drug classification in modern psychiatry.

[The origin and success of neuroleptics]. / Naissance et prospérité des neuroleptiques

The authors retrace the origin and the development of the idea of neurolepsy in anesthesiology, first under the influence of Laborit, and in psychiatry, under the influence of Delay and Deniker, during the early 1950's. In these two fields, neuroleptic drugs were considered contrary to ideas and practice at that time and disturbed current ideas.

[Neuroplegia: results of an interdisciplinary approach to its physiopathology]. / La neuroplégie: résultats d'une approche interdisciplinaire de la physio-pathologie

Neuroplegia was born from a physiopathological study of states of shock and research on inhibition of the autonomic reaction to aggression. Over the last 25 years, the experimental facts have become accumulated in favour of the first theory of H. Laborit, i.e. that this so-called defence reaction defended our lives only through conservation of motor activity in the environment. When this motor activity is inefficacious or useless, the neuroendocrine reaction may lead, during the acute phase, to states of shock and to chronic psychosomatic pathology. On this general theme, inhibition of this reaction by neuroplegic drugs, among which the phenothiazine derivatives have played a very important role, has led in numerous surgical and medical disciplines, to basic research and therapeutic consequences. Thus, in anesthetics, it was at the origin of potentialised anesthesia, then neuroleptanalgesia. In general intensive care, it is used in various ways in the study and treatment of states of shock. In psychiatry, it has initiated neuro-psychopharmacology and the neuro-physiological and biochemical study of the nervous system in its response to the psycho-social environment. It has found its place in anesthesia and in obstetric pathology. But above all, has led pharmacologists to the study of metabolic and biochemical activities. The result of an interdisciplinary approach, neuroplegia has on the contrary, often been the origin of an interdisciplinary development of our physiological and physiopathological knowledge. Today this development seems to better understand its mode of action at various levels of organisation of living systems. One may thus say that neuroplegia, apart from its therapeutic interest, has been a good working instrument and led to better understanding of numerous biological disciplines.