Exploring venlafaxine pharmacokinetic variability with a phenotyping approach, a multicentric french-swiss study (MARVEL study).

It is well known that the standard doses of a given drug may not have equivalent effects in all patients. To date, the management of depression remains mainly empirical and often poorly evaluated. The development of a personalized medicine in psychiatry may reduce treatment failure, intolerance or resistance, and hence the burden and costs of mood depressive disorders. The Geneva Cocktail Phenotypic approach presents several advantages including the "in vivo" measure of different cytochromes and transporter P-gp activities, their simultaneous determination in a single test, avoiding the influence of variability over time on phenotyping results, the administration of low dose substrates, a limited sampling strategy with an analytical method developed on DBS analysis. The goal of this project is to explore the relationship between the activity of drug-metabolizing enzymes (DME), assessed by a phenotypic approach, and the concentrations of Venlafaxine (VLX) + O-demethyl-venlafaxine (ODV), the efficacy and tolerance of VLX. This study is a multicentre prospective non-randomized open trial. Eligible patients present a major depressive episode, MADRS over or equal to 20, treatment with VLX regardless of the dose during at least 4 weeks. The Phenotype Visit includes VLX and ODV concentration measurement. Following the oral absorption of low doses of omeprazole, midazolam, dextromethorphan, and fexofenadine, drug metabolizing enzymes activity is assessed by specific metabolite/probe concentration ratios from a sample taken 2 h after cocktail administration for CYP2C19, CYP3A4, CYP2D6; and by the determination of the limited area under the curve from the capillary blood samples taken 2-3 and 6 h after cocktail administration for CYP2C19 and P-gp. Two follow-up visits will take place between 25 and 40 days and 50-70 days after inclusion. They include assessment of efficacy, tolerance and observance. Eleven french centres are involved in recruitment, expected to be completed within approximately 2 years with 205 patients. Metabolic ratios are determined in Geneva, Switzerland. By showing an association between drug metabolism and VLX concentrations, efficacy and tolerance, there is a hope that testing drug metabolism pathways with a phenotypical approach would help physicians in selecting and dosing antidepressants. The MARVEL study will provide an important contribution to increasing the knowledge of VLX variability and in optimizing the use of methods of personalized therapy in psychiatric settings. ClinicalTrials.gov NCT02590185 (10/27/2015). This study is currently recruiting participants

Sémiologie et diagnostics psychiatriques : un couple moderne enrichi par la phénoménologie

L’objectif annoncé de E. Husserl lorsqu’il élabore la phénoménologie est celui d’une science rigoureuse de l’expérience humaine. Les psychiatres qui ont affaire aux expériences de leurs patients, celles-ci ne pouvant être réduites à une sommation de symptômes cliniques ou de processus biologiques, se sont alors naturellement rapprochés de la phénoménologie, en particulier dans la deuxième moitié du XXe siècle. Néanmoins, la phénoménologie est actuellement une approche relativement marginale en psychiatrie, en comparaison des neurosciences, des approches cognitivistes ou encore de la psychanalyse. Pour autant, elle reste plus que jamais compatible avec une approche multidisciplinaire de la psychiatrie, en particulier parce qu’elle cherche à décrire le ‘comment’ de l’expérience humaine, là où d’autres disciplines recherchent principalement le ‘pourquoi’. En outre, la phénoménologie a pu s’enrichir de ses interactions avec les neurosciences sous la forme du courant de la neurophénoménologie qui vise une interaction mutuellement générative entre les deux disciplines. De manière générale, l’approche moderne de la phénoménologie psychiatrique doit permettre non seulement de dépasser l’approche purement symptomatique du DSM ou de la CIM pour se plonger au cœur de l’expérience vécue en décrivant les structures du vécu des patients mais aussi d’enrichir les autres disciplines de la psychiatrie et d’être enrichie par celles-ci en retour. Nous montrerons comment la phénoménologie peut éclairer la psychopathologie et offrir des pistes de réflexion en clinique et en recherche, en prenant certains exemples récents sur la dépression et la schizophrénie.</jats:p

Cardiophenomenology: a refinement of neurophenomenology II - an experiential-empirical inquiry of the surprise reaction in depression with preliminary results

Cardiophenomenology aims at extending, and partly reforming, the neuro-phenomenological approach of Francisco Varela, as a new paradigm on the joint-basis of Edmund Husserl's a priori conceptual dynamics of the living present (Husserl E; 1991) and an experiment of anticipatory time-dynamics of visual motor perception (Varela FJ; 1996). In order to do so, we situate this new paradigm at the cardio-vascular level of the emotional dynamics of the lived experience and thus refine the combining of the first- and third-person analysis. In a first 2019 article on "Cardiophenomenology: a refinement of neurophenomenology" (Depraz N, Desmidt T; 2019), we presented and argued for the theoretical hypothesis of cardiophenomenology, which centralizes the heart system as a core, intrinsic part of the cognitive system. The latter in turn needs to be enlarged in order to include a cardiac-affective dimension. In the present article, we aim to show how to do cardiophenomenology with the example of 4 participants, two with depression and two healthy controls, and we implement it by applying the core-hypothesis of Varela's co-generative methodology. We present preliminary results indicating how cardiophenomenology can be generatively applied, in this instance in the case of the surprise reaction of individuals with and without depression, who take part in an emotional task. This co-generative application of cardiophenomenology, its being effectively and fruitfully practiced, is as such a main result of the article 1. since neurophenomenology remains a speculative hypothesis, the applicability and practicability of which is still till now hardly demonstrated. Our additional goal 2. is also here to describe the psychopathological mechanisms underlying emotional reactivity in depression more accurately. In this regard, without going in detail into the results which will be presented in the article, we can observe that individuals with depression are not necessarily "hypo-reactive" to surprise as it is commonly stated in the psychopathological scientific literature, as in the case for melancholic, resp. catatonic states, but might be hyper-reactive with strong associated emotional rhythms, which may refer to another kind of depression named anxious depression. On the theoretical philosophical level proper finally, another result 3. concerns the very micro-dynamic of surprise during the emotional task: we argue here for an understanding of surprise non-limited to an abstract shock but encompassing the whole process of expectation and reaction after the shock. With such a global understanding in mind, we show the presence of gradual forms of cognitive mechanisms with continuities between the individuals undergoing depressive states and the ones who do not. This leads in turn to consider depression as being more multifaceted and more continuous with non-depressive states than initially thought

Etude de la connotation des mots utilisés en odontologie chez les dentistes et les non-dentistes

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