Thérèse Lempérière : ses travaux sur les psychotropes et perspectives actuelles.

Résumé Thérèse Lempérière a accompagné l’émergence de la psychopharmacologie. Ses travaux concernent autant l’efficacité des psychotropes (antidépresseurs, neuroleptiques) sur les différents symptômes que l’induction de symptômes par certaines substances psychotropes (amphétamine, psilocybine). Ou encore l’étude des effets neurologiques des neuroleptiques et l’analyse de l’apport des traitements retards. Son regard sur la pharmacologie est celui d’une clinicienne et reste en cela très actuel : l’analyse fine clinique des effets des psychotropes sur le psychisme et le système nerveux central, qui a initialement permis d’affiner les indications des molécules, continue à être aujourd’hui la principale source permettant d’améliorer la connaissance en psychiatrie et sciences de la cognition, mais aussi et surtout de rechercher de nouvelles pistes thérapeutiques, au-delà des catégories diagnostiques et en dehors de leur indication première, ou de rechercher la meilleure adéquation du profil thérapeutique à un profil clinique. Objectives This paper is a tribute to Thérèse Lempérière's legacy regarding the study of psychotropic substances and an analysis of the lessons from her work for the future of psychopharmacology. Materials and methods All her historical papers, mainly published in French journals, were reviewed as well as the summary of “titles and works” written by her. Rather than a comprehensive review, we have selected some papers in order to cover the various domains she addressed and to highlight some main characteristics of her work and envision. The paper also analyze her work in the context of the remarkable progresses of psychopharmacology in the second part of the 20th century as well as new perspectives for future innovations. Results Thérèse Lempérière started studying psychotropic drugs in 1953, in the department where the antipsychotic effects of chlorpromazine were discovered. In the same line as these pioneering observations, her work widely covers the study of various compounds, with a specific interest for clinical descriptions of therapeutic effects in patients of new drugs as well as induction of symptoms by substance of abuse in patients or healthy volunteers. She explored every classes of the classification proposed by J. Delay in 1957 (adopted by the 1961 World Congress of Psychiatry) i.e. psycholeptics including neuroleptics and mood stabilizers, psychoanaleptics such as nooanaleptics (amphetamine) and thymoanaleptics (antidepressants) and psychodysleptics especially psilocybine. Regarding amphetamine, T. Lempérière discussed the differential diagnosis between pharmacopsychose and what she called ‘amphetaminic pseudopsychosis’ when psychosis persist after withdrawal and proposed that amphetamine reveals previously quiescent predisposition to schizophrenia. She underlined the bidirectional relation: amphetamine induces psychosis but also amphetamine as a self-medication for early dysfunction of schizophrenia. A picture very similar to current view on cannabis precipitated psychosis or self-medication by cocaine. T. Lempérière studied several classes of antidepressant from the early tricyclic to very recent ones. In the ‘two-year of experience with imipramine’ article, she reviewed the best indications and factors of good response (melancholia, simple depression, women) while imipramine has low efficacy in severe melancholia and hypochondria. She proposed the association of imipramine to reduce the number of ECT and indicate some efficacy in OCD. The descriptions of psilocybine in healthy volunteers and patients are full of information regarding the individual variability and the semiology of psychotic-like experiences induced by psilocybine (illusions, “hallucinose”, pseudohallucinations rather than hallucinations). Of course, Thérèse Lempérière's explored the neuroleptics, many of them, with a special focus to analyze the differential therapeutic profile of each molecule, in order to improve the adequacy to the patient's profile. A main contribution was the study of reserpine, starting in 1954, that, together with the observation with chlorpromazine, contributed to the definition the of neuroleptics’ class. These included the presence of extra pyramidal signs, which Thérèse Lempérière also explored, including tardive dyskinesia. She rapidly recommended to prescribe neuroleptic at the minimal efficient dose and to avoid systematic prescription of anticholinergic drug. Thérèse Lempérière promoted the use of long acting neuroleptics early in the disease, since they prevent treatment interruption and facilitate the alliance. Regarding the mood stabilizers, Thérèse Lempérière contributed to the introduction of valpromide and valproate in psychiatry. Conclusions Thérèse Lempérière is a pioneer woman in French Psychiatry, and her legacy is not restricted to the field of psychopharmacology. Her remarkable contribution is mainly due to her clinical vision and analysis. The overview of the Thérèse Lempérière's contribution to psychopharmacology underline several features of the early history of psychopharmacology: the origin of psychotropic drugs out of neurosciences (antibacterial, antiparasitic, antihypertensive, etc.), the close relation between clinician and chemists from pharmaceutical company, rapid transfer to the clinic and rapid feedback to the pharmaceutical companies, the fine clinical (phenotypic) descriptions, the use of psychotropic drugs to dissect psychiatric syndromes. These are invaluable lessons to apply for the future developments of psychopharmacology. They plead for a reinforcement of translational psychiatry with always more bidirectional relations between clinics and basic sciences and advocate for reopening the borders between psychiatry and other medical disciplines. [ABSTRACT FROM AUTHOR]