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1. Relationship between childhood physical abuse and clinical severity of treatment-resistant depression in a geriatric population.

Author

Antoine Yrondi, Christophe Arbus, Djamila Bennabi, Thierry D'Amato, Frank Bellivier, Thierry Bougerol, Vincent Camus, Philippe Courtet, Olivier Doumy, Jean-Baptiste Genty, Jérôme Holtzmann, Mathilde Horn, Christophe Lancon, Marion Leboyer, Pierre-Michel Llorca, Julia Maruani, Rémi Moirand, Fanny Molière, Jean Petrucci, Raphaelle Richieri, Ludovic Samalin, Florian Stephan, Guillaume Vaiva, Michel Walter, FondaMental Advanced Centres of Expertise in Resistant Depression (FACE-DR) Collaborators, Emmanuel Haffen, Bruno Aouizerate, and Wissam El-Hage

Subjects
Medicine, Science
Abstract

IntroductionWe assessed the correlation between childhood maltreatment (CM) and severity of depression in an elderly unipolar Treatment-Resistant Depression (TRD) sample.MethodsPatients were enrolled from a longitudinal cohort (FACE-DR) of the French Network of Expert TRD Centres.ResultsOur sample included 96 patients (33% of the overall cohort) aged 60 years or above, with a mean age of 67.2 (SD = 5.7). The majority of the patients were female (62.5%). The Montgomery and Asberg Depression Rating Scale (MADRS) and Quick Inventory Depression Scale-Self Report (QIDS-SR) mean scores were high, 28.2 (SD = 7.49) [MADRS score range: 0-60; moderate severity≥20, high severity≥35] and 16.5 (SD = 4.94) [IDS-SR score range: 0-27; moderate severity≥11, high severity≥16], respectively. Mean self-esteem scores were 22.47 (SD = 6.26) [range 0-30]. In an age- and sex-adjusted model, we found a positive correlation between childhood trauma (CTQ scores) and depressive symptom severity [MADRS (β = 0.274; p = 0.07) and QIDS-SR (β = 0.302; p = 0.005) scores]. We detected a statistically significant correlation between physical abuse and depressive symptom severity [MADRS (β = 0.304; p = 0.03) and QIDS-SR (β = 0.362; p = 0.005) scores]. We did not observe any significant correlation between other types of trauma and depressive symptom severity. We showed that self-esteem (Rosenberg scale) mediated the effect of physical abuse (PA) on the intensity of depressive symptoms [MADRS: b = 0.318, 95% BCa C.I. [0.07, 0.62]; QIDS-SR: b = 0.177, 95% BCa C.I. [0.04, 0.37]]. Preacher & Kelly's Kappa Squared values of 19.1% (k2 = 0.191) and 16% (k2 = 0.16), respectively for the two scales, indicate a moderate effect.ConclusionTo our knowledge, this is the first study conducted in a geriatric TRD population documenting an association between childhood trauma (mainly relating to PA) and the intensity of depressive symptoms.

Published
2021
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2. Exploring venlafaxine pharmacokinetic variability with a phenotyping approach, a multicentric french-swiss study (MARVEL study)

Author

Célia Lloret-Linares, Youssef Daali, Sylvie Chevret, Isabelle Nieto, Fanny Molière, Philippe Courtet, Florence Galtier, Raphaëlle-Marie Richieri, Sophie Morange, Pierre-Michel Llorca, Wissam El-Hage, Thomas Desmidt, Frédéric Haesebaert, Philippe Vignaud, Jerôme Holtzmann, Jean-Luc Cracowski, Marion Leboyer, Antoine Yrondi, Fabienne Calvas, Liova Yon, Philippe Le Corvoisier, Olivier Doumy, Kyle Heron, Damien Montange, Siamak Davani, Julien Déglon, Marie Besson, Jules Desmeules, Emmanuel Haffen, and Frank Bellivier

Subjects
Therapeutics. Pharmacology, RM1-950, Toxicology. Poisons, RA1190-1270
Abstract

Abstract Background 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. Methods/design 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. Discussion 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. Trial registration ClinicalTrials.gov NCT02590185 (10/27/2015). This study is currently recruiting participants.

Published
2017
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3. Treatment-Resistant Depression in a Real-World Setting: First Interim Analysis of Characteristics, Healthcare Resource Use, and Utility Values of the FondaMental Cohort

Author

Antoine Yrondi, Djamila Bennabi, Emmanuel Haffen, Delphine Quelard, Ludovic Samalin, Julia Maruani, Etienne Allauze, Damien Pierre, Thierry Bougerol, Vincent Camus, Thierry D’Amato, Olivier Doumy, Jérôme Holtzmann, Christophe Lançon, Fanny Moliere, Rémi Moirand, Isabel Nieto, Raphaëlle Marie Richieri, Mathilde Horn, Laurent Schmitt, Florian Stephan, Jean-Baptiste Genty, Guillaume Vaiva, Michel Walter, Philippe Courtet, Marion Leboyer, Pierre-Michel Llorca, Sophie Marguet, Nathalie Dennis, Dominique Schaetz, Wissam El-Hage, and Bruno Aouizerate

Subjects
treatment-resistant depression, real-world, utility, healthcare resource use, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Background: Major depressive disorder (MDD) is among the most common psychiatric disorders. One-third of patients are usually unresponsive to several lines of treatment. This study aimed to describe the FondaMental French cohort of patients with treatment-resistant depression (TRD) and to estimate utility and healthcare resource use outcomes. Methods: Patients with TRD were evaluated prospectively over four years (baseline, 6, 12, 18, 24, 36 and 48 months) in a real-world clinical setting. Interim analyses focused on the first two consecutive years. Four MDD-related states (major depressive episode (MDE), response, remission, recovery) were defined based on the MADRS (Montgomery–Åsberg depression rating scale) and other clinical events. Health status was assessed with the EuroQol 5 Dimensions 5 Level (EQ-5D-5L) questionnaire. Utility values were estimated as preference measures that the patients assigned to their overall health status. Results: This study was based on 252 patients with TRD. The mean utility value by health state was 0.41, 0.63, 0.80, and 0.90, for MDE, response, remission, and recovery, respectively. At baseline, 59% of patients had an MADRS score of at least 28. Their baseline average utility value was lower compared to the other patients (0.43 versus 0.58, p < 0.001). This significant difference persisted at the following visits. The rate of patients in MDEs having at least one hospitalisation for depression or other reasons than depression was generally higher than that in the other health states. Conclusion: This study documented patterns in healthcare resource consumption, quality of life, and other characteristics in patients with TRD, both globally and by health state and depression severity.

Published
2020
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4. Assessment of Translocator Protein Density, as Marker of Neuroinflammation, in Major Depressive Disorder: A Pilot, Multicenter, Comparative, Controlled, Brain PET Study (INFLADEP Study)

Author

Antoine Yrondi, Bruno Aouizerate, Wissam El-Hage, Fanny Moliere, Claire Thalamas, Nicolas Delcourt, Marie Sporer, Simon Taib, Laurent Schmitt, Nicolas Arlicot, Deborah Meligne, Agnes Sommet, Anne S. Salabert, Sebastien Guillaume, Philippe Courtet, Florence Galtier, Denis Mariano-Goulart, Nicolas Menjot De Champfleur, Emmanuelle Le Bars, Thomas Desmidt, Mathieu Lemaire, Vincent Camus, Maria J. Santiago-Ribeiro, Jean P. Cottier, Philippe Fernandez, Marie Meyer, Vincent Dousset, Olivier Doumy, Didier Delhaye, Lucile Capuron, Marion Leboyer, Emmanuel Haffen, Patrice Péran, Pierre Payoux, and Christophe Arbus

Subjects
depressive disorder, depression, neuroinflammation, inflammation, TSPO, DPA-714, Psychiatry, RC435-571
Abstract

Background: Major depressive disorder (MDD) is a serious public health problem with high lifetime prevalence (4.4–20%) in the general population. The monoamine hypothesis is the most widespread etiological theory of MDD. Also, recent scientific data has emphasized the importance of immuno-inflammatory pathways in the pathophysiology of MDD. The lack of data on the magnitude of brain neuroinflammation in MDD is the main limitation of this inflammatory hypothesis. Our team has previously demonstrated the relevance of [18F] DPA-714 as a neuroinflammation biomarker in humans. We formulated the following hypotheses for the current study: (i) Neuroinflammation in MDD can be measured by [18F] DPA-714; (ii) its levels are associated with clinical severity; (iii) it is accompanied by anatomical and functional alterations within the frontal-subcortical circuits; (iv) it is a marker of treatment resistance.Methods: Depressed patients will be recruited throughout 4 centers (Bordeaux, Montpellier, Tours, and Toulouse) of the French network from 13 expert centers for resistant depression. The patient population will be divided into 3 groups: (i) experimental group—patients with current MDD (n = 20), (ii) remitted depressed group—patients in remission but still being treated (n = 20); and, (iii) control group without any history of MDD (n = 20). The primary objective will be to compare PET data (i.e., distribution pattern of neuroinflammation) between the currently depressed group and the control group. Secondary objectives will be to: (i) compare neuroinflammation across groups (currently depressed group vs. remitted depressed group vs. control group); (ii) correlate neuroinflammation with clinical severity across groups; (iii) correlate neuroinflammation with MRI parameters for structural and functional integrity across groups; (iv) correlate neuroinflammation and peripheral markers of inflammation across groups.Discussion: This study will assess the effects of antidepressants on neuroinflammation as well as its role in the treatment response. It will contribute to clarify the putative relationships between neuroinflammation quantified by brain neuroimaging techniques and peripheral markers of inflammation. Lastly, it is expected to open innovative and promising therapeutic perspectives based on anti-inflammatory strategies for the management of treatment-resistant forms of MDD commonly seen in clinical practice.Clinical trial registration (reference: NCT03314155): https://www.clinicaltrials.gov/ct2/show/NCT03314155?term=neuroinflammation&cond=depression&cntry=FR&rank=1

Published
2018
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5. Significant Need for a French Network of Expert Centers Enabling a Better Characterization and Management of Treatment-Resistant Depression (Fondation FondaMental)

Author

Antoine Yrondi, Djamila Bennabi, Emmanuel Haffen, Marion Garnier, Frank Bellivier, Thierry Bourgerol, Vincent Camus, Thierry D’Amato, Olivier Doumy, Frédéric Haesebaert, Jérôme Holtzmann, Christophe Lançon, Philippe Vignaud, Fanny Moliere, Isabel Nieto, Raphaëlle Marie Richieri, Philippe Domenech, Corentin Rabu, Luc Mallet, Liova Yon, Laurent Schmitt, Florian Stephan, Guillaume Vaiva, Michel Walter, Pierre-Michel Llorca, Philippe Courtet, Marion Leboyer, Wissam El-Hage, and Bruno Aouizerate

Subjects
treatment-resistant depression, depressive disorder, assessment, network, innovative strategies, Psychiatry, RC435-571
Abstract

BackgroundMajor depression is characterized by (i) a high lifetime prevalence of 16–17% in the general population; (ii) a high frequency of treatment resistance in around 20–30% of cases; (iii) a recurrent or chronic course; (iv) a negative impact on the general functioning and quality of life; and (v) a high level of comorbidity with various psychiatric and non-psychiatric disorders, high occurrence of completed suicide, significant burden along with the personal, societal, and economic costs. In this context, there is an important need for the development of a network of expert centers for treatment-resistant depression (TRD), as performed under the leadership of the Fondation FondaMental.MethodsThe principal mission of this national network is to establish a genuine prevention, screening, and diagnosis policy for TRD to offer a systematic, comprehensive, longitudinal, and multidimensional evaluation of cases. A shared electronic medical file is used referring to a common exhaustive and standardized set of assessment tools exploring psychiatric, non-psychiatric, metabolic, biological, and cognitive dimensions of TRD. This is paralleled by a medico-economic evaluation to examine the global economic burden of the disease and related health-care resource utilization. In addition, an integrated biobank has been built by the collection of serum and DNA samples for the measurement of several biomarkers that could further be associated with the treatment resistance in the recruited depressed patients. A French observational long-term follow-up cohort study is currently in progress enabling the extensive assessment of resistant depressed patients. In those unresponsive cases, each expert center proposes relevant therapeutic options that are classically aligned to the international guidelines referring to recognized scientific societies.DiscussionThis approach is expected to improve the overall clinical assessments and to provide evidence-based information to those clinicians most closely involved in the management of TRD thereby facilitating treatment decisions and choice in everyday clinical practice. This could contribute to significantly improve the poor prognosis, the relapsing course, daily functioning and heavy burden of TRD. Moreover, the newly created French network of expert centers for TRD will be particularly helpful for a better characterization of sociodemographic, clinical, neuropsychological, and biological markers of treatment resistance required for the further development of personalized therapeutic strategies in TRD.

Published
2017
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6. Recommendations of the treatment-resistant depression expert center network for promoting tobacco smoking cessation based on the results from the real-world FACE-TRD national cohort

Author

Alexandra Garosi, Christelle Andrieu-Haller, Olivier Doumy, Nicolas Suc, Julia Maruani, J.-B. Genty, Martin Breyton, Raphaëlle Richieri, Frank Bellivierid, Antoine Yrondid, Mathilde Horn, T Korchia, Guillaume Fond, Laurent Boyers, Rémi Moirand, Bruno Aouizerate, Jean Petrucci, Christophe Arbus, Michel Walter, Thierry Bougerol, Jérôme Holtzmann, Philippe Courtet, Vincent Camus, Christophe Lançon, Guillaume Vaiva, Pierre-Michel Llorca, Fanny Moliere, Djamila Bennabi, Wissam El-Hage, Florian Stephan, Mélanie Faugere, Ludovic Samalin, Romain Rey, Ophélia Godin, Marion Leboyer, Emmanuel Haffen, Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), Aix Marseille Université (AMU), Aix-Marseille Université - École de médecine (AMU SMPM MED), Aix-Marseille Université - Faculté des sciences médicales et paramédicales (AMU SMPM), Aix Marseille Université (AMU)-Aix Marseille Université (AMU), Fondation FondaMental [Créteil], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université Bourgogne Franche-Comté [COMUE] (UBFC), Neurobiologie et Psychiatrie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Laboratoire Sciences Cognitives et Sciences Affectives - UMR 9193 (SCALab), and Université de Lille-Centre National de la Recherche Scientifique (CNRS)

Subjects
Male, medicine.medical_treatment, MESH: Tobacco Smoking, Suicide, Attempted, tobacco, MESH: Nicotine, Cohort Studies, Depressive Disorder, Treatment-Resistant, chemistry.chemical_compound, Surveys and Questionnaires, Medicine, Precision Medicine, Varenicline, MESH: Cohort Studies, Depression (differential diagnoses), health care economics and organizations, education.field_of_study, public mental health, MESH: Middle Aged, MESH: Suicidal Ideation, public health, Middle Aged, MESH: Smoking Cessation, psychiatry, Cohort, depression, MESH: Suicide, Attempted, Female, mental health, Nicotine, medicine.medical_specialty, Population, education, MESH: Precision Medicine, smoking, Suicidal Ideation, MESH: Depressive Disorder, Treatment-Resistant, Sex Factors, MESH: Sex Factors, Tobacco Smoking, Humans, MESH: Surveys and Questionnaires, Psychiatry, Biological Psychiatry, Pharmacology, MESH: Humans, Suicide attempt, business.industry, Odds ratio, medicine.disease, MESH: Male, schizophrenia, chemistry, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Smoking cessation, Smoking Cessation, business, Treatment-resistant depression, MESH: Female
Abstract

Background Tobacco smoking has been associated with suicide, impulsivity and depression in non-clinical populations with differences across sexes. Objective To determine the role of tobacco smoking in Treatment-Resistant Depression (TRD) according to sex in a precision-medicine approach. Method The FACE-TRD cohort is a national cohort of TRD patients recruited in 13 resistant depression expert centers between 2014 and 2021 and followed-up at 6 months. A standardized one-day long comprehensive battery was carried out, including trained-clinician and patient-reported outcomes, and patients were reevaluated at 6 months on their smoking and psychiatric hospitalization outcomes. Results 355 TRD participants were included (222 women). The smoking rate was much higher in TRD women compared to the French general population (34% vs 24%) while it was comparable for men (approximately 29%). In multivariate analyses, compared to non-smoking women, female smokers had significantly increased number of lifetime psychiatric hospitalizations (standardized beta B = 0.232, p = 0.014) and electro-convulsive therapy (adjusted odds ratio (aOR) = 2.748, p = 0.005), increased suicidal ideations (aOR = 4.047, p = 0.031), history of suicide attempt (aOR = 1.994, p = 0.033), and increased impulsivity (B = 0.210, p = 0.006) and were more frequently treated by benzodiazepines (aOR = 1.848, p = 0.035) and third- or fourth-line TRD treatments (antipsychotics aOR = 2.270, p = 0.006, mood stabilizers aOR = 2.067 p = 0.044). Tobacco smoking at baseline was predictive of psychiatric hospitalization within 6 months in persistent smoking women (aOR = 2.636, p = 0.031). These results were not replicated in men, for whom tobacco smoking was only associated with increased clinician-rated and self-reported depressive symptoms (respectively B = 0.207, p = 0.022 and B = 0.184, p = 0.048). The smoking cessation rate at 6 months was higher in women than in men (12% vs. 7%). No patient was administered nicotine substitute or varenicline at the two timepoints. Interpretation Combining these results and those of the literature, we recommend that active tobacco cessation should be promoted in TRD to improve depression, suicide and impulsivity especially in women. Female smokers appear as a specific population with heavier mental health outcomes that should be specifically addressed.

Published
2022

7. Childhood Trauma increases suicidal behaviour in a treatment-resistant depression population: a FACE-DR report

Author

Antoine Yrondi, Guillaume Vaiva, Michel Walter, Thierry D Amato, Frank Bellivier, Djamila Bennabi, Thierry Bougerol, Vincent Camus, Olivier Doumy, Jean-Baptiste Genty, Emmanuel Haffen, Jérôme Holtzmann, Mathilde Horn, Christophe Lançon, Marion Leboyer, Pierre-Michel Llorca, Julia Maruani, Rémi Moirand, Fanny Molière, Jean Petrucci, Raphaelle Richieri, Ludovic Samalin, Laurent Schmitt, Florian Stephan, Philippe Courtet, Wissam El-Hage, Bruno Aouizerate, B. Aouizerate, D. Bennabi, M. Leboyer, E. Haffen, P.M. Llorca, V. Barteau, S. Bensalem, H. Laouamri, Karmene Souryis, L. Mallet, L. Yon, J. Petrucci, J.B. Genty, A. Yrondi, D. Pierre, L. Schmitt, M. Sarrail, I. Ryff, E. Beuchet, G. Tio, C. Cappe, E. Clerc, M. Garnier, R.M. Honciuc, E. Allauze, O. Blanc, F. Bellivier, N. Allaili, I. Nieto, J. Meheust, Y. Sunthavy, J. Maruani, T. Bougerol, M. Polosan, P. Courvoisier, J. Holtzmann, B. Fredembach, S. Foubert-Andreani, V. Camus, W. El Hage, T. D’Amato, F. Haesebaert, C. Dubien, M. Lefebvre, A. Meznad, J. Brunelin, R. Moirand, O. Doumy, C. Lancon, R. Richieri, P. Peri, M. Faugere, C. Faget-Agius, P. Courtet, J.P. Boulenger, F. Moliere, F. Stephan, M. Walter, C. Mesmeur, G. Vaiva, M. Horn, Fondation FondaMental [Créteil], Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Toulouse Neuro Imaging Center (ToNIC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hopital de Bohars - CHRU Brest (CHU - BREST ), Soins Primaires, Santé Publique, Registre des cancers de Bretagne Occidentale (SPURBO), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Centre de recherche en neurosciences de Lyon (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier le Vinatier [Bron], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Centre d'Investigation Clinique de Besançon (Inserm CIC 1431), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Laboratoire de Neurosciences Intégratives et Cliniques - UFC (EA 481) (NEURO), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), CHU Grenoble, Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d’Investigation Clinique [Tours] CIC 1415 (CIC ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Charles Perrens, Nutrition et Neurobiologie intégrée (NutriNeuro), Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux-Ecole nationale supérieure de chimie, biologie et physique-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHU Henri Mondor, Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), CHU Clermont-Ferrand, Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux (NPsy-Sydo), CHU Clermont-Ferrand-Université Clermont Auvergne (UCA), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Soins Primaires, Santé Publique, Registre des cancers de Bretagne Occidentale (EA7479 SPURBO), Université de Brest (UBO)-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), Laboratoire de Neurosciences Intégratives et Cliniques - UFC (UR 481) (NEURO), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hospitalier Charles Perrens [Bordeaux], CHU Henri Mondor [Créteil], CHU Clermont-Ferrand-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), and Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)

Subjects
Depressive disorders, MESH: Depression, MESH: Violence, Population, Poison control, Violence, Suicide prevention, Childhood trauma, MESH: Depressive Disorder, Treatment-Resistant, Suicidal Ideation, Depressive Disorder, Treatment-Resistant, 03 medical and health sciences, 0302 clinical medicine, MESH: Risk Factors, Risk Factors, Rating scale, Surveys and Questionnaires, Humans, Medicine, MESH: Surveys and Questionnaires, Risk factor, education, Suicidal ideation, Childhood neglect, Biological Psychiatry, education.field_of_study, MESH: Humans, MESH: Suicidal Ideation, Depression, business.industry, Childhood abuse, CTQ tree, 3. Good health, 030227 psychiatry, Suicide, Psychiatry and Mental health, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Treatment-resistant depression, medicine.symptom, Columbia Suicide Severity Rating Scale, business, 030217 neurology & neurosurgery, Clinical psychology
Abstract

International audience; Objective: In addition to heredity, exposure to early-life adversity is an important predisposing risk factor of suicidal behaviour. Although the association between Childhood Trauma (CT) and suicide risk is well documented, interactions between CT and suicidal behaviour in Treatment-Resistant Depression (TRD) populations have received little coverage. This study aimed to evaluate i) association between CT and suicidal behaviour in a TRD population, and ii) the role of personality traits and impulsiveness as potential factors of mediation in these associations.Methods: Patients were recruited from a cohort of the French network of TRD expert centers. Depressive symptom severity, CT, suicidal behaviour, personality traits, and impulsiveness were assessed with the Montgomery-Åsberg Depression Rating Scale (MADRS), the Childhood Trauma Questionnaire (CTQ), the Columbia Suicide Severity Rating Scale (CSSRS), the Structured Clinical Interview for DSM-IV, the Big Five Inventory, and the Barratt Impulsivness Scale (BIS) respectively.Results: Among the 256 patients with a baseline CTQ, in relation to suicide risk for the current depressive episode, we found an association with the total CTQ scores mediated by the intensity of the current episode in a model adjusted for age and sex (total effect: β = 0.171; p = 0.011, direct effect: β = 0.135; p = 0.043; indirect effect: β = 0.036; p = 0.048). Focusing on CT subtypes, we detected an association between suicide risk and physical neglect in a model adjusted for age and sex (β = 0.301; p = 0.002), without any mediation by the intensity of the current episode. There was no mediation effect from personality traits nor impulsiveness. With regards to CSSRS to assess suicidal ideation, we did not find any association with the total CTQ score and CT subtype scores.Conclusion: We report a strong association between suicidal behaviour and CT (in particular childhood physical neglect) in a TRD population.

Published
2021

8. [Current nosographic classifications of anxiety disorders]

Author

Alexandra, Bouvard, Olivier, Doumy, Thomas, Bienvenu, and Bruno, Aouizerate

Subjects
Stress Disorders, Post-Traumatic, Obsessive-Compulsive Disorder, Phobic Disorders, Humans, Panic Disorder, Agoraphobia, Anxiety Disorders
Abstract

CURRENT NOSOGRAPHIC CLASSIFICATIONS TOF ANXIETY DISORDERS. Anxiety disorders are psychiatric pathologies covering a wide range of clinical entities that are characterized by a pathological anxiety leading to severe emotional distress and marked impairment in daily functioning. They primarily differentiate from each other according to the general content of concerns, and originally included the panic disorder with or without agoraphobia, specific phobias, social anxiety disorder, generalized anxiety disorder, obsessive-compulsive disorder and post-traumatic stress disorder. However, the 5th edition of the Diagnostic and Statistical Manual of Mental Disorders introduced the classification of anxiety disorders into three separate subcategories in 2013, mainly comprising the anxiety disorders themselves (panic disorder with or without agoraphobia, specific phobia, social anxiety disorder and generalized anxiety disorder), obsessive- compulsive disorder and post-traumatic stress disorder on the basis of their respective clinical, psychological and pathophysiological determinants.NOSOGRAPHIE ACTUELLE DES TROUBLES ANXIEUX. Les troubles anxieux sont des pathologies recouvrant diverses entités, ayant en commun une anxiété pathologique responsable d’une souffrance et d’une altération significative du fonctionnement. Ils se différencient les uns des autres essentiellement par le contenu des préoccupations qu’ils génèrent, et comprenaient originellement le trouble panique avec ou sans agoraphobie, les phobies spécifiques, le trouble d’anxiété sociale, le trouble anxiété généralisée, le trouble obsessionnel-compulsif et le trouble de stress post-traumatique. Néanmoins, la 5e édition du Manuel diagnostique et statistique des troubles mentaux (DSM-5) les classent à partir de 2013 en trois groupes distincts incluant les troubles anxieux proprement dits (trouble panique avec ou sans agoraphobie, phobies spécifiques, trouble d’anxiété sociale et trouble d’anxiété généralisée), le trouble obsessionnel-compulsif et le trouble de stress post-traumatique sur la base de leurs principaux déterminants.

Published
2020

9. Childhood maltreatment and clinical severity of treatment‐resistant depression in a French cohort of outpatients (FACE‐DR): One‐year follow‐up

Author

Raphaëlle Richieri, Jean B. Genty, Djamila Bennabi, Guillame Vaiva, Pierre M. Llorca, Laurent Schmitt, Thierry Bougerol, Fanny Moliere, Marion Leboyer, Philippe Courtet, Thierry d'Amato, Michel Walter, Gustavo Turecki, Emmanuel Haffen, Frank Bellivier, Julia Maruani, Bruno Aouizerate, Ludovic Samalin, Mathilde Horn, Antoine Yrondi, J. Holtzmann, Wissam El-Hage, Florian Stephan, Rémi Moirand, Jean Petrucci, Olivier Doumy, Vincent Camus, Christophe Lançon, Fondation FondaMental [Créteil], Pôle neurosciences [Hôpital de Purpan - Toulouse], CHU Toulouse [Toulouse], Hôpital Charles Perrens, Nutrition et Neurobiologie intégrée (NutriNeuro), Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux-Ecole nationale supérieure de chimie, biologie et physique-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre d'Investigation Clinique de Besançon (Inserm CIC 1431), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Laboratoire de Neurosciences Intégratives et Cliniques - UFC (UR 481) (NEURO), Université de Franche-Comté (UFC), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier le Vinatier [Bron], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Service de Psychiatrie [CHRU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Hôpital Michel Fontan 1, Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d’Investigation Clinique [Tours] CIC 1415 (CIC ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), IMRB - 'Neuropsychiatrie translationnelle' [Créteil] (U955 Inserm - UPEC), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Pôle de Psychiatrie [Hôpital Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital H. Mondor - A. Chenevier, CHU Clermont-Ferrand, Hopital de Bohars - CHRU Brest (CHU - BREST ), Douglas Mental Health University Institute [Montréal], McGill University = Université McGill [Montréal, Canada], Centre National de Ressources et de Résilience [Lille] (CN2R), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Laboratoire de Neurosciences Intégratives et Cliniques - UFC (EA 481) (NEURO), Centre de recherche en neurosciences de Lyon (CRNL), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Michel Fontan 1-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10

Subjects
medicine.medical_specialty, Depressive disorders, MESH: Depression, Population, MESH: Depressive Disorder, Major, Poison control, Childhood trauma, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Surveys and Questionnaires, MESH: Child, Outpatients, medicine, Humans, Child Abuse, Prospective Studies, MESH: Surveys and Questionnaires, education, Prospective cohort study, Child, Childhood neglect, education.field_of_study, Depressive Disorder, Major, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, MESH: Humans, business.industry, Depression, Antidepressant response, Childhood abuse, CTQ tree, MESH: Follow-Up Studies, MESH: Child Abuse, medicine.disease, MESH: Prospective Studies, 3. Good health, 030227 psychiatry, MESH: Outpatients, Psychiatry and Mental health, Clinical Psychology, Sexual abuse, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Cohort, Major depressive disorder, Treatment-resistant depression, business, 030217 neurology & neurosurgery, Follow-Up Studies
Abstract

International audience; Childhood maltreatment is associated with major depressive disorder (MDD). It not only increases the risk of lifetime MDD, but it also aggravates its course. Among depressed patients, 20-30% of them experience treatment-resistance depression (TRD). We aimed to assess the association between childhood maltreatment, severity of depression in a unipolar TRD sample, and patient outcomes after one-year of follow-up. Methods: Patients were recruited for a prospective cohort from the French network of TRD expert centers. Depressive symptom severity was assessed with the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Quick Inventory of Depressive Symptomatology self-report (QIDS-SR). Childhood maltreatment was evaluated with the Childhood Trauma Questionnaire (CTQ).Results: In total, 256 patients filled in the CTQ at baseline between 2012 and 2019. At baseline, the MADRS score was associated with CTQ score (β = .185; p = .004). QIDS was also associated with CTQ scores (β = .27; p < .001). Regarding the different subtypes of childhood maltreatment, MADRS was associated with physical (β = .21; p = .005) and sexual abuse (β = .22; p = .002), while QIDS with physical abuse (β = .304; p < .001) and physical neglect (β = .254; p < .001). However, we did not find any significant association focusing on the other types of traumas. During a 1-year follow-up focusing on remission, CTQ scores (baseline) were less important in remittent patients [n = 38; CTQ score = 39.26 (9.68)] than in nonremittent ones [n = 92; CTQ score = 46.02 (17.53)] (p = .027). There was no significant difference among remitters and nonremitters based on trauma subtypes. At baseline, CTQ scores had a significant influence on remission at 1 year (χ2 (1) = 5.57; p < .05). We lost this influence adding MADRS scores at baseline in the model (p = .063).Conclusion: We highlighted a significant association between the severity of depressive disorders and childhood maltreatment in the TRD population. Information about a history of childhood maltreatment helps in identifying individuals who could be less likely to go into remission after treatment.

Published
2020

10. Association between anhedonia and suicidal events in patients with mood disorders: A 3-year prospective study

Author

Rémi Moirand, Sébastien Gard, Frank Bellivier, Julia Maruani, Joséphine Loftus, Pierre-Michel Llorca, Jonathan Dubois, Philippe Courtet, Chantal Henry, Etienne Allauze, Wissam El-Hage, Marion Leboyer, Jean-Baptiste Genty, Raoul Belzeaux, Olivier Doumy, Jérôme Holtzmann, Jean-Pierre Kahn, Valerie Aubin, Guillaume Vaiva, Thierry Bougerol, Djamila Bennabi, Vincent Camus, Laurent Schmitt, Michel Walter, Christophe Lançon, Thierry d'Amato, Ludovic Samalin, Bruno Etain, Raphaëlle Richieri, Mathilde Horn, Emilie Olié, Caroline Dubertret, Fanny Moliere, Florian Stephan, Emmanuel Haffen, Antoine Yrondi, Jean-Michel Azorin, Bruno Aouizerate, Isabelle Jaussent, Julien Dubreucq, Mircea Polosan, Christine Passerieux, Déborah Ducasse, Institut Pascal (IP), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA)-Institut national polytechnique Clermont Auvergne (INP Clermont Auvergne), Université Clermont Auvergne (UCA)-Université Clermont Auvergne (UCA), and Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)

Subjects
Anhedonia, media_common.quotation_subject, Suicide, Attempted, behavioral disciplines and activities, Suicide prevention, Pleasure, Suicidal Ideation, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, medicine, Humans, Prospective Studies, Suicidal ideation, ComputingMilieux_MISCELLANEOUS, media_common, Suicide attempt, business.industry, Mood Disorders, Odds ratio, medicine.disease, 030227 psychiatry, Psychiatry and Mental health, Clinical Psychology, Mood disorders, Marital status, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], medicine.symptom, business, 030217 neurology & neurosurgery, Clinical psychology
Abstract

Background As almost all mental disorders are associated with increased suicidal-related behavior, anhedonia might be a trans-diagnostic dimension to target for suicide prevention. Methods For this 3-year-long prospective study, 2,839 outpatients with mood disorders were recruited. They were divided in: (a) two groups according to the occurrence or not of suicidal ideation during the follow-up, and (b) two groups according to the occurrence or not of suicide attempts during the follow-up. Anhedonia was assessed using a composite score (the French version of the 14-item Snaith-Hamilton Pleasure Scale and item 13 of the Quick Inventory of Depressive Symptomatology scale) at inclusion and at 6, 12, 24, and 36 months after inclusion. Results Patients with mood disorders and anhedonia at least at one follow-up visit had a 1.4-fold higher risk of suicidal ideation (adjusted odds ratio = 1.35; 95% confidence interval [1.07, 1.70]), even after adjustment for confounding factors of suicide risk (i.e., bipolar or unipolar disorder, sex, age, marital status, education level, antidepressant intake, personal history of suicide attempt, at least one childhood trauma, and mean of the maximum depression score during the follow-up). Conversely, association between anhedonia and suicide attempt did not remain significant after adjustment. Conclusions The significant association between anhedonia and suicide ideation in patients with mood disorders stresses the need of targeting hedonia in mood disorders, and of research focusing on the position to pleasure in life through eudaimonia.

Published
2020

11. Treatment-resistant depression in a real-world setting: first interim analysis of characteristics, healthcare resource use, and utility values of the fondaMental cohort

Author

Pierre-Michel Llorca, Sophie Marguet, Raphaëlle Richieri, Vincent Camus, Dominique Schaetz, Emmanuel Haffen, Antoine Yrondi, Christophe Lançon, Jean-Baptiste Genty, Mathilde Horn, Julia Maruani, Thierry Bougerol, Marion Leboyer, Djamila Bennabi, Philippe Courtet, Rémi Moirand, Nathalie Dennis, Laurent Schmitt, Etienne Allauze, Isabel Nieto, Wissam El-Hage, Jérôme Holtzmann, Damien Pierre, Fanny Moliere, Florian Stephan, Guillaume Vaiva, Olivier Doumy, Michel Walter, Ludovic Samalin, Thierry d'Amato, Bruno Aouizerate, Delphine Quelard, Fondation FondaMental [Créteil], Toulouse Neuro Imaging Center (ToNIC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Laboratoire de Neurosciences Intégratives et Cliniques - UFC (UR 481) (NEURO), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre d'Investigation Clinique de Besançon (Inserm CIC 1431), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Janssen-Cilag [Issy-les-Moulineaux], CHU Clermont-Ferrand, Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier le Vinatier [Bron], Nutrition et Neurobiologie intégrée (NutriNeuro), Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux-Ecole nationale supérieure de chimie, biologie et physique-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre hospitalier Charles Perrens [Bordeaux], Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hopital de Bohars - CHRU Brest (CHU - BREST ), Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Amaris, Herrada, Anthony, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Laboratoire de Neurosciences Intégratives et Cliniques - UFC (EA 481) (NEURO), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), CHU Toulouse [Toulouse], Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Hôpital Charles Perrens, Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
medicine.medical_specialty, real-world, [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Article, lcsh:RC321-571, 03 medical and health sciences, 0302 clinical medicine, healthcare resource use, Quality of life, Rating scale, Internal medicine, Medicine, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Major depressive episode, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Depression (differential diagnoses), business.industry, General Neuroscience, medicine.disease, Interim analysis, 3. Good health, 030227 psychiatry, utility, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Cohort, treatment-resistant depression, Major depressive disorder, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, medicine.symptom, business, Treatment-resistant depression, 030217 neurology & neurosurgery
Abstract

Background: Major depressive disorder (MDD) is among the most common psychiatric disorders. One-third of patients are usually unresponsive to several lines of treatment. This study aimed to describe the FondaMental French cohort of patients with treatment-resistant depression (TRD) and to estimate utility and healthcare resource use outcomes. Methods: Patients with TRD were evaluated prospectively over four years (baseline, 6, 12, 18, 24, 36 and 48 months) in a real-world clinical setting. Interim analyses focused on the first two consecutive years. Four MDD-related states (major depressive episode (MDE), response, remission, recovery) were defined based on the MADRS (Montgomery&ndash, &Aring, sberg depression rating scale) and other clinical events. Health status was assessed with the EuroQol 5 Dimensions 5 Level (EQ-5D-5L) questionnaire. Utility values were estimated as preference measures that the patients assigned to their overall health status. Results: This study was based on 252 patients with TRD. The mean utility value by health state was 0.41, 0.63, 0.80, and 0.90, for MDE, response, remission, and recovery, respectively. At baseline, 59% of patients had an MADRS score of at least 28. Their baseline average utility value was lower compared to the other patients (0.43 versus 0.58, p &lt, 0.001). This significant difference persisted at the following visits. The rate of patients in MDEs having at least one hospitalisation for depression or other reasons than depression was generally higher than that in the other health states. Conclusion: This study documented patterns in healthcare resource consumption, quality of life, and other characteristics in patients with TRD, both globally and by health state and depression severity.

Published
2020

12. Clinical guidelines for the management of depression with specific comorbid psychiatric conditions French recommendations from experts (the French Association for Biological Psychiatry and Neuropsychopharmacology and the fondation FondaMental)

Author

C. Rabu, Wissam El-Hage, Isabel Nieto, Emmanuel Haffen, Antoine Yrondi, P. Courtet, Marion Leboyer, Franck Bellivier, Najib Allaïli, Guillaume Vaiva, Fanny Moliere, Jean-Michel Dorey, J.-B. Genty, Frédéric Haesebaert, Sylvie Lancrenon, Olivier Doumy, Djamila Bennabi, Laurent Schmitt, Florian Stephan, Bruno Aouizerate, Thierry Bougerol, C. Lançon, S. Destouches, Michel Walter, Raphaëlle Richieri, Thomas Charpeaud, J. Holtzmann, Pierre-Michel Llorca, M. Lefebvre, Vincent Camus, Centre d'expertise de la performance Gilles Cometti [Dijon] (CEP), Université de Bourgogne (UB), Sylia Stat Lancrenon S.A.S., Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7), Fondation FondaMental [Créteil], Clinique Psychiatrique Universitaire, Departement de Psychiatrie, Hôpital de la Conception [CHU - APHM] (LA CONCEPTION ), Deutsches Elektronen-Synchrotron [Zeuthen] (DESY), Helmholtz-Gemeinschaft, Laboratoire de Neurosciences Fonctionnelles et Pathologies (LNFP), Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Laboratoire de Neurosciences Intégratives et Cliniques - UFC (EA 481) (NEURO), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université de Franche-Comté (UFC), Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux - Clermont Auvergne (NPsy-Sydo), CHU Clermont-Ferrand-Université Clermont Auvergne (UCA), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Groupe d'étude des proliférations lymphoïdes (GPL), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), ERL 6230, Centre National de la Recherche Scientifique (CNRS), Helmholtz-Gemeinschaft = Helmholtz Association, Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), and Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)

Subjects
Male, Psychopharmacology, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Comorbidity, Scientific evidence, 0302 clinical medicine, Elderly, lcsh:Psychiatry, 030212 general & internal medicine, Depression (differential diagnoses), ComputingMilieux_MISCELLANEOUS, Psychiatry, Anxiety disorders, Major depressive disorder, Pharmacotherapy, Substance use disorders, [SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, 3. Good health, Neuropsychopharmacology, Psychiatry and Mental health, Practice Guidelines as Topic, Female, France, Biological psychiatry, Management of depression, Foundations, Research Article, medicine.medical_specialty, Substance-Related Disorders, lcsh:RC435-571, Personality Disorders, 03 medical and health sciences, medicine, Humans, Association (psychology), Expert Testimony, Biological Psychiatry, Aged, Depressive Disorder, Major, business.industry, [SCCO.NEUR]Cognitive science/Neuroscience, medicine.disease, Personality disorders, 030227 psychiatry, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Substance use, business
Abstract

International audience; Background Recommendations for pharmacological treatments of major depression with specific comorbid psychiatric conditions are lacking. Method The French Association for Biological Psychiatry and Neuropsychopharmacology and the fondation FondaMental developed expert consensus guidelines for the management of depression based on the RAND/UCLA Appropriatneness Method. Recommendations for lines of treatment are provided by the scientific committee after data analysis and interpretation of the results of a survey of 36 psychiatrist experts in the field of major depression and its treatments. Results The expert guidelines combine scientific evidence and expert clinician's opinion to produce recommendations for major depression with comorbid anxiety disorders, personality disorders or substance use disorders and in geriatric depression. Conclusion These guidelines provide direction addressing common clinical dilemmas that arise in the pharmacologic treatment of major depression with comorbid psychiatric conditions.

Published
2019

13. Prevalence of Metabolic Syndrome and Associated Factors in a Cohort of Individuals With Treatment-Resistant Depression: Results From the FACE-DR Study

Author

Ophélia, Godin, Djamila, Bennabi, Antoine, Yrondi, Raphaelle, Richieri, Thierry, D'Amato, Franck, Bellivier, Thierry, Bougerol, Mathilde, Horn, Vincent, Camus, Philippe, Courtet, Olivier, Doumy, Jean Baptiste, Genty, Wissam, El-Hage, Frederic, Haesebaert, Jerôme, Holtzmann, Christophe, Lancon, Marion, Leboyer, Pierre Michel, Llorca, Julia, Maruani, Fanny, Molière, Ludovic, Samalin, Laurent, Schmitt, Florian, Stephan, Guillaume, Vaiva, Michel Walter Bruno, Aouizerate, and Emmanuel, Haffen

Subjects
Adult, Male, medicine.medical_specialty, Population, Comorbidity, Cohort Studies, 03 medical and health sciences, Depressive Disorder, Treatment-Resistant, 0302 clinical medicine, Risk Factors, Internal medicine, medicine, Prevalence, Humans, education, Major depressive episode, Depression (differential diagnoses), Metabolic Syndrome, education.field_of_study, Depressive Disorder, Major, business.industry, Middle Aged, medicine.disease, 3. Good health, 030227 psychiatry, Psychiatry and Mental health, Cohort, Female, France, medicine.symptom, business, Treatment-resistant depression, 030217 neurology & neurosurgery, Dyslipidemia, Cohort study
Abstract

BACKGROUND: The aim of this study was to estimate the prevalence of metabolic syndrome (MetS) and its components in a cohort of French patients with treatment-resistant depression (TRD) and to determine correlations with sociodemographic, clinical, and treatment-related factors. METHODS: From 2012 to 2018, 205 patients who met DSM-IV criteria for major depressive episode with moderate-to-severe symptoms (Montgomery-Asberg Depression Rating Scale score ≥ 20), and at least Stage II resistance according to Thase and Rush criteria were enrolled in the FondaMental Advanced Centers of Expertise in Resistant Depression (FACE-DR) cohort. Data on sociodemographic and clinical characteristics, lifestyle information, and treatment and comorbidities were collected, and a blood sample was drawn. MetS was defined according to the criteria of the International Diabetes Federation. RESULTS: Overall, 38% of individuals with TRD met criteria for MetS. The frequency of MetS was significantly higher in men than in women only for patients aged 40 years or older (46.3% vs 35.2%, P = .0427). Moreover, whereas the management for diabetes was good, less than one-third of the patients with high blood pressure or dyslipidemia were treated for these conditions. Multivariate analysis showed that individuals with abnormal plasma c-reactive protein levels had a 3-fold increased risk (95% CI, 1.5-5.2) of having MetS, independent of other potential confounders. CONCLUSION: The prevalence of MetS is higher in patients with TRD than in those with other psychiatric disorders and characterized by a considerable undertreatment of some components of MetS in this population. Diagnosis and treatment of the components of MetS should be systematically performed to prevent the occurrence of cardiovascular diseases in patients with TRD. These findings highlight the need for integrated care, with more interaction and coordination between psychiatrists and primary care providers.

Published
2019

14. Clinical guidelines for the management of treatment-resistant depression: French recommendations from experts, the French Association for Biological Psychiatry and Neuropsychopharmacology and the fondation FondaMental

Author

S. Destouches, Fanny Moliere, Sylvie Lancrenon, J. Holtzmann, Wissam El-Hage, Raphaëlle Richieri, Thomas Charpeaud, Bruno Aouizerate, Laurent Schmitt, Olivier Doumy, M. Lefebvre, Marion Leboyer, C. Lançon, N. Alaïli, Emmanuel Haffen, Michel Walter, C. Rabu, Isabel Nieto, Frédéric Haesebaert, Guillaume Vaiva, Thierry Bougerol, Djamila Bennabi, J.-B. Genty, P.-M. Llorca, Vincent Camus, Antoine Yrondi, Jean-Michel Dorey, P. Courtet, Franck Bellivier, Florian Stephan, Centre d'Investigation Clinique de Besançon (Inserm CIC 1431), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), CHU Clermont-Ferrand, Toulouse Neuro Imaging Center (ToNIC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Fondation FondaMental [Créteil], Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Nutrition et Neurobiologie intégrée (NutriNeuro), Université Bordeaux Segalen - Bordeaux 2-Institut National de la Recherche Agronomique (INRA)-Université Sciences et Technologies - Bordeaux 1 (UB)-Institut Polytechnique de Bordeaux-Ecole nationale supérieure de chimie, biologie et physique, Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), Université de Montpellier (UM), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Departement de Psychiatrie, Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Laboratoire de Neurosciences Fonctionnelles et Pathologies (LNFP), Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Laboratoire de Neurosciences Intégratives et Cliniques - UFC (UR 481) (NEURO), Université de Franche-Comté (UFC), El-Hage, Wissam, Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche en neurosciences de Lyon (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux-Ecole nationale supérieure de chimie, biologie et physique-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Laboratoire de Neurosciences Intégratives et Cliniques - UFC (EA 481) (NEURO), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université Bordeaux Segalen - Bordeaux 2-Institut National de la Recherche Agronomique (INRA)-Université Sciences et Technologies - Bordeaux 1-Institut Polytechnique de Bordeaux-Ecole nationale supérieure de chimie, biologie et physique

Subjects
Male, medicine.medical_specialty, Psychopharmacology, lcsh:RC435-571, [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Resistance (psychoanalysis), Antidepressants, Expert consensus guidelines, Major depressive disorder, Pharmacotherapy, Treatment resistant depression, Scientific evidence, 03 medical and health sciences, Depressive Disorder, Treatment-Resistant, 0302 clinical medicine, lcsh:Psychiatry, medicine, Humans, 030212 general & internal medicine, Psychiatry, Association (psychology), Expert Testimony, Depression (differential diagnoses), Biological Psychiatry, Depressive Disorder, Major, medicine.disease, Antidepressive Agents, 3. Good health, 030227 psychiatry, Neuropsychopharmacology, Psychiatry and Mental health, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Practice Guidelines as Topic, Female, France, Biological psychiatry, Psychology, Treatment-resistant depression, Research Article, Foundations
Abstract

Background Clear guidance for successive antidepressant pharmacological treatments for non-responders in major depression is not well established. Method Based on the RAND/UCLA Appropriateness Method, the French Association for Biological Psychiatry and Neuropsychopharmacology and the fondation FondaMental developed expert consensus guidelines for the management of treatment-resistant depression. The expert guidelines combine scientific evidence and expert clinicians’ opinions to produce recommendations for treatment-resistant depression. A written survey comprising 118 questions related to highly-detailed clinical presentations was completed on a risk-benefit scale ranging from 0 to 9 by 36 psychiatrist experts in the field of major depression and its treatments. Key-recommendations are provided by the scientific committee after data analysis and interpretation of the results of the survey. Results The scope of these guidelines encompasses the assessment of pharmacological resistance and situations at risk of resistance, as well as the pharmacological and psychological strategies in major depression. Conclusion The expert consensus guidelines will contribute to facilitate treatment decisions for clinicians involved in the daily assessment and management of treatment-resistant depression across a number of common and complex clinical situations. Electronic supplementary material The online version of this article (10.1186/s12888-019-2237-x) contains supplementary material, which is available to authorized users.

Published
2019

15. Dépression résistante : les autres stratégies thérapeutiques

Author

Marion Leboyer, Wissam El-Hage, Pierre-Michel Llorca, Maxime Bubrovszky, Olivier Doumy, Pierre Courvoisier, Vincent Camus, Christophe Lançon, Raphaëlle Richieri, Marion Garnier, Isabel Nieto, Thomas Charpeaud, Najib Allaïli, Thierry Bougerol, Bruno Aouizerate, Djamila Bennabi, Guillaume Vaiva, Ghassen Saba, Emmanuel Haffen, Jérôme Holtzmann, Thierry d'Amato, Rémy Bation, Fanny Moliere, Philippe Courtet, Frank Bellivier, Frédéric Haesebaert, INSERM U955, équipe 15, Service de psychiatrie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier-Réseau de coopération scientifique en santé mentale, Fondation FondaMental [Créteil]-Fondation FondaMental [Créteil]-Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Fondation FondaMental [Créteil], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier le Vinatier [Bron], Laboratoire de Neurosciences Intégratives et Cliniques - UFC (UR 481) (NEURO), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Laboratoire de santé publique évaluation des systèmes de soins et santé perçue, Département Universitaire de Psychiatrie - [Hôpital Sainte Marguerite - APHM] (Hôpitaux Sud), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), Pôle Psychiatrie et Neurologie [Grenoble], Centre Hospitalier Universitaire [Grenoble] (CHU), Service de Psychiatrie [CHRU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Hôpital Michel Fontan 1, UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), CHU Clermont-Ferrand, Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Hôpital Charles Perrens, Clinique Psychiatrique Universitaire [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Centre hospitalier Charles Perrens [Bordeaux]

Subjects
Drug, Pramipexole, Methylphenidate, business.industry, [SDV]Life Sciences [q-bio], media_common.quotation_subject, Modafinil, Antagonist, General Medicine, Pharmacology, 3. Good health, 030227 psychiatry, 03 medical and health sciences, 0302 clinical medicine, medicine, Antidepressant, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Ketamine, business, ComputingMilieux_MISCELLANEOUS, 030217 neurology & neurosurgery, Depression (differential diagnoses), media_common, medicine.drug
Abstract

Non-selective and irreversible MAOI have become as third or fourth-line strategy for the management of treatment-resistant depression. Non-selective and irreversible MAOI requires careful monitoring of drug interactions and dietary restrictions. Nutritional supplements such as omega-3 have been found to produce beneficial effects in the management of treatment-resistant depression when administered in combination with the ongoing antidepressant treatment. The glutamate antagonist ketamine has been found to produce beneficial effects in the management of treatment-resistant depression while administered alone. Dopamine and/or norepinephrine agonists, such as methylphenidate, modafinil or pramipexole, have been found to produce beneficial effects in the management of treatment-resistant depression when administered in combination with the ongoing antidepressant treatment.

Published
2016

16. Quelle définition pour la dépression résistante ?

Author

Rémy Bation, Guillaume Vaiva, Fanny Moliere, Frank Bellivier, Frédéric Haesebaert, Pierre-Michel Llorca, Vincent Camus, Christophe Lançon, Raphaëlle Richieri, Marion Leboyer, Thomas Charpeaud, Wissam El-Hage, Isabel Nieto, Jérôme Holtzmann, Pierre Courvoisier, Emmanuel Haffen, Najib Allaïli, Thierry d'Amato, Bruno Aouizerate, Olivier Doumy, Marion Garnier, Maxime Bubrovszky, Ghassen Saba, Thierry Bougerol, Djamila Bennabi, Philippe Courtet, Fondation FondaMental [Créteil], Pôle Psychiatrie et Neurologie [Grenoble], Centre Hospitalier Universitaire [Grenoble] (CHU), Laboratoire de santé publique évaluation des systèmes de soins et santé perçue, Département Universitaire de Psychiatrie - [Hôpital Sainte Marguerite - APHM] (Hôpitaux Sud), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), INSERM U955, équipe 15, Service de psychiatrie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier-Réseau de coopération scientifique en santé mentale, Fondation FondaMental [Créteil]-Fondation FondaMental [Créteil]-Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier le Vinatier [Bron], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Variabilité de réponse aux Psychotropes (VariaPsy - U1144), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Neurosciences Intégratives et Cliniques - UFC (UR 481) (NEURO), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Service de Psychiatrie [CHRU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Hôpital Michel Fontan 1, UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), CHU Clermont-Ferrand, Centre hospitalier Charles Perrens [Bordeaux], Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Clinique Psychiatrique Universitaire [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Hôpital Charles Perrens

Subjects
medicine.medical_specialty, Psychometrics, business.industry, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Chronic pain, General Medicine, Drug resistance, medicine.disease, Comorbidity, 030227 psychiatry, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, Electroconvulsive therapy, Quality of life, medicine, Antidepressant, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], business, Intensive care medicine, ComputingMilieux_MISCELLANEOUS, 030217 neurology & neurosurgery, Depression (differential diagnoses)
Abstract

The most largely used definition of the treatment-resistant depression relies on the failure of two successive trials of antidepressant treatment at an adequate dose and duration. The absence of response to previous antidepressant treatments should be assessed using specific and appropriate clinical instruments enabling a correct staging of the therapeutic resistance. A wide range of socio-demographic and clinical factors (i.e. psychiatric/somatic comorbidities) are classically associated with the therapeutic resistance. The aim of the treatment of major depression is to achieve a complete clinical remission. The presence of residual symptoms increases the risk for the subsequent occurrence of relapses and recurrences, hence facilitating the development of therapeutic resistance. The treatment-resistant depression has a deleterious impact on the social, familial or professional functioning, thereby leading to an impaired quality of life with serious socioeconomic consequences and costs.

Published
2016

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

Author

Philippe Le Corvoisier, Jules Alexandre Desmeules, Célia Lloret-Linares, Jean-Luc Cracowski, Wissam El-Hage, L. Yon, Kyle Heron, Frank Bellivier, Frédéric Haesebaert, Siamak Davani, Damien Montange, Thomas Desmidt, Olivier Doumy, Antoine Yrondi, Fanny Moliere, Raphaëlle-Marie Richieri, Philippe Vignaud, Sophie Morange, Marie Besson, Sylvie Chevret, Isabelle Nieto, Marion Leboyer, Jérôme Holtzmann, F. Galtier, Fabienne Calvas, Julien Déglon, Pierre-Michel Llorca, Emmanuel Haffen, Philippe Courtet, Youssef Daali, Biostatistique et épidemiologie clinique, Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Pathologies du système nerveux : recherche épidémiologique et clinique, Université Montpellier 1 ( UM1 ) -IFR76-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre de pharmacologie et innovation dans le diabète ( CPID ), Université Montpellier 1 ( UM1 ) -Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ) -Centre National de la Recherche Scientifique ( CNRS ), Centre d'Investigation Clinique ( CIC ), Hospices Civils de Lyon ( HCL ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -CHU de Lyon, Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux - Clermont Auvergne ( NPsy-Sydo ), CHU Clermont-Ferrand-Université Clermont Auvergne ( UCA ), Clinique Psychiatrique Universitaire [Tours], CHRU Tours, Imagerie et cerveau, Université de Tours-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Hypoxie : Physiopathologie Respiratoire et Cardiovasculaire ( HP2 ), Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service de psychiatrie, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier, Institut Mondor de Recherche Biomédicale ( IMRB ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), CIC - CHU Henri Mondor, Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ), UR 1341 Alimentation et adaptations digestives, nerveuses et comportementales, Institut National de la Recherche Agronomique ( INRA ) -Alimentation Humaine ( ALIM.H ) -Alimentation et adaptations digestives, nerveuses et comportementales ( ADNC ), Cognition, Action, et Plasticité Sensorimotrice [Dijon - U1093] ( CAPS ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Geneva University Hospital (HUG), Service de biostatistique et information médicale de l’hôpital Saint Louis (Equipe ECSTRA) (SBIM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut national du cancer [Boulogne] (INCA)-Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP), Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Assistance Publique - Hôpitaux de Marseille (APHM), CHU Clermont-Ferrand, Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux (NPsy-Sydo), CHU Clermont-Ferrand-Université Clermont Auvergne (UCA), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre d’Investigation Clinique [Tours] CIC 1415 (CIC ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche en neurosciences de Lyon (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Laval [Québec] (ULaval), Centre Hospitalier Universitaire [Grenoble] (CHU), Centre d'Investigation Clinique [Grenoble] (CIC Grenoble ), CHU Grenoble-Hôpital Michallon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier, Fondation FondaMental [Créteil], CHU Toulouse [Toulouse], Toulouse Neuro Imaging Center (ToNIC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Centre d'investigation clinique de Toulouse (CIC 1436), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Investigation Clinique Henri Mondor (CIC Henri Mondor), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Bordeaux [Bordeaux], University of Bristol [Bristol], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Lausanne University Hospital, Cognition, Action, et Plasticité Sensorimotrice [Dijon - U1093] (CAPS), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), CHU Clermont-Ferrand-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Pôle Santé publique et médecine publique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Pôle Santé publique et médecine publique [CHU Toulouse], Douhairie, Marie-Laurence, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10

Subjects
Male, Oncology, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [SDV.NEU.PC] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, Venlafaxine, Pharmacology, 030226 pharmacology & pharmacy, ATP-Binding Cassette, Sub-Family B, Member 1/metabolism, Adolescent, Adult, Aged, Aged, 80 and over, Antidepressive Agents, Second-Generation/blood, Antidepressive Agents, Second-Generation/pharmacokinetics, Antidepressive Agents, Second-Generation/therapeutic use, Cytochrome P-450 CYP2C19/metabolism, Cytochrome P-450 CYP2D6/metabolism, Cytochrome P-450 CYP3A/metabolism, Depressive Disorder, Major/drug therapy, Depressive Disorder, Major/metabolism, Female, France, Genotype, Humans, Middle Aged, Phenotype, Switzerland, Treatment Outcome, Venlafaxine Hydrochloride/blood, Venlafaxine Hydrochloride/pharmacokinetics, Venlafaxine Hydrochloride/therapeutic use, Young Adult, Study Protocol, [ SDV.NEU.SC ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, 0302 clinical medicine, 80 and over, Cytochrome P-450 CYP3A, Medicine, Pharmacology (medical), Major depressive episode, ComputingMilieux_MISCELLANEOUS, ddc:615, ddc:617, [SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, Venlafaxine Hydrochloride, Area under the curve, [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, Antidepressive Agents, 3. Good health, Cytochrome P-450 CYP2D6, [ SDV.NEU.NB ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [ SCCO.NEUR ] Cognitive science/Neuroscience, Antidepressive Agents, Second-Generation, medicine.symptom, medicine.drug, CYP2D6, medicine.medical_specialty, Major/drug therapy/metabolism, CYP2C19, [ SDV.NEU.PC ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, 03 medical and health sciences, Pharmacokinetics, lcsh:RA1190-1270, Internal medicine, Member 1/metabolism, ATP Binding Cassette Transporter, Subfamily B, Member 1, Dosing, lcsh:Toxicology. Poisons, Second-Generation/blood/pharmacokinetics/therapeutic use, Depressive Disorder, Depressive Disorder, Major, Sub-Family B, business.industry, [SCCO.NEUR]Cognitive science/Neuroscience, lcsh:RM1-950, [SCCO.NEUR] Cognitive science/Neuroscience, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Cytochrome P-450 CYP2C19, lcsh:Therapeutics. Pharmacology, Venlafaxine Hydrochloride/blood/pharmacokinetics/therapeutic use, ATP-Binding Cassette, Personalized medicine, business, [SDV.NEU.SC] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, 030217 neurology & neurosurgery
Abstract

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.

Published
2017

18. Prise en charge des troubles dépressifs résistants : recommandations françaises formalisées par des experts de l’AFPBN et de la fondation FondaMental

Author

Fanny Moliere, P. Courtet, Bruno Aouizerate, Franck Bellivier, Pierre-Michel Llorca, Isabel Nieto, Emmanuel Haffen, Djamila Bennabi, Wissam El-Hage, Marie-Noëlle Lefebvre, Guillaume Vaiva, Raphaëlle Richieri, Thomas Charpeaud, Florian Stephan, Vincent Camus, Olivier Doumy, Thierry d'Amato, Frédéric Haesebaert, Jean-Baptiste Genty, S. Destouches, Michel Walter, C. Lançon, N. Alaïli, Jérôme Holtzmann, Laurent Schmitt, Antoine Yrondi, Sylvie Lancrenon, Thierry Bougerol, Marion Leboyer, Groupe d'étude des proliférations lymphoïdes (GPL), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), ONERA - The French Aerospace Lab [Palaiseau], ONERA-Université Paris Saclay (COmUE), Departement de Psychiatrie, Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Laboratoire Image, Ville, Environnement [Strasbourg] (LIVE), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Deutsches Elektronen-Synchrotron [Zeuthen] (DESY), Helmholtz-Gemeinschaft = Helmholtz Association, Laboratoire de Neurosciences Fonctionnelles et Pathologies (LNFP), Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Laboratoire de Neurosciences Intégratives et Cliniques - UFC (UR 481) (NEURO), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux (NPsy-Sydo), CHU Clermont-Ferrand-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Groupe d'étude des proliférations lymphoïdes ( GPL ), Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), ONERA - The French Aerospace Lab ( Palaiseau ), ONERA, Hôpital de la Conception [CHU - APHM] ( LA CONCEPTION ), Laboratoire Image, Ville, Environnement [Strasbourg] ( LIVE ), Université de Strasbourg ( UNISTRA ), Deutsches Elektronen-Synchrotron [Zeuthen] ( DESY ), Helmholtz-Gemeinschaft, Laboratoire de Neurosciences Fonctionnelles et Pathologies ( LNFP ), Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique ( CNRS ), Centre Hospitalier Régional Universitaire de Tours ( CHRU TOURS ), Laboratoire de Neurosciences Intégratives et Cliniques - UFC ( NEURO ), Université Bourgogne Franche-Comté ( UBFC ) -Université de Franche-Comté ( UFC ), Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux - Clermont Auvergne ( NPsy-Sydo ), CHU Clermont-Ferrand-Université Clermont Auvergne ( UCA ), Université de Strasbourg (UNISTRA), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Laboratoire de Neurosciences Intégratives et Cliniques - UFC (EA 481) (NEURO), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), and Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-CHU Clermont-Ferrand

Subjects
medicine.medical_specialty, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Population, Disease, [ SDV.NEU.PC ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, 03 medical and health sciences, Indirect costs, [ SDV.NEU.SC ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, 0302 clinical medicine, Quality of life (healthcare), Arts and Humanities (miscellaneous), medicine, Psychiatry, education, Depression (differential diagnoses), ComputingMilieux_MISCELLANEOUS, education.field_of_study, [SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, business.industry, [SCCO.NEUR]Cognitive science/Neuroscience, [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, 3. Good health, 030227 psychiatry, Neuropsychopharmacology, Psychiatry and Mental health, Brain stimulation, [ SDV.NEU.NB ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [ SCCO.NEUR ] Cognitive science/Neuroscience, Biological psychiatry, business, 030217 neurology & neurosurgery
Abstract

Major depression represents among the most frequent psychiatric disorders in the general population with an estimated lifetime prevalence of 16-17%. It is characterized by high levels of comorbidities with other psychiatric conditions or somatic diseases as well as a recurrent or chronic course in 50 to 80% of the cases leading to negative repercussions on the daily functioning, with an impaired quality of life, and to severe direct/indirect costs. Large cohort studies have supported that failure of a first-line antidepressant treatment is observed in more than 60% of patients. In this case, several treatment strategies have been proposed by classical evidence-based guidelines from internationally recognized scientific societies, referring primarily on: I) the switch to another antidepressant of the same or different class; II) the combination with another antidepressant of complementary pharmacological profile; III) the addition of a wide range of pharmacological agents intending to potentiate the therapeutic effects of the ongoing antidepressant medication; IV) the association with appropriate psychological therapies; and, V) the use of non-invasive brain stimulation techniques. However, although based on the most recently available data and rigorous methodology, standard guidelines have the significant disadvantage of not covering a large variety of clinical conditions, while currently observed in everyday clinical practice. From these considerations, formalized recommendations by a large panel of French experts in the management of depressed patients have been developed under the shared sponsorship of the French Association of Biological Psychiatry and Neuropsychopharmacology (AFPBN) and the Fondation FondaMental. These French recommendations are presented in this special issue in order to provide relevant information about the treatment choices to make, depending particularly on the clinical response to previous treatment lines or the complexity of clinical situations (clinical features, specific populations, psychiatric comorbidities, etc.). Thus, the present approach will be especially helpful for the clinicians enabling to substantially facilitate and guide their clinical decision when confronted to difficult-to-treat forms of major depression in the daily clinical practice. This will be expected to significantly improve the poor prognosis of the treatment-resistant depression thereby lowering the clinical, functional and costly impact owing directly to the disease.

Published
2017

19. Spectre du trouble obsessionnel-compulsif revisité à travers un bipôle impulsion-compulsion

Author

Olivier Doumy and Bruno Aouizerate

Subjects
medicine.medical_specialty, business.industry, Flexibility (personality), Cognition, General Medicine, Disease, medicine.disease, Comorbidity, Impulse control, Body dysmorphic disorder, medicine, Spectrum disorder, Psychiatry, business
Abstract

Key points The so-called obsessive-compulsive spectrum disorder (OCD spectrum) is represented by a large variety of clinical entities. There are in general obsessive-compulsive disorder, trichotillomania or Gilles de la Tourette disease among the impulse control disorders, body dysmorphic disorder and hypochondriasis among the somatoform disorders. Updated overview of the OCD spectrum through a bipolar configuration with the impulsion-compulsion (I-C) spectrum, characterized by a failure to resist and control intrusive thoughts associated with repetitive behaviors that seem to be uncontrollable or require considerable efforts to suppress their execution. There are several disrupted processes in the I-C spectrum, including cognitive control, flexibility and behavioural inhibition. All these psychiatric affections demonstrated to share apparent similarities regarding clinical symptomatology, demographic considerations, comorbidity and course pattern, and responses to the serotonine reuptake inhibitors and cognitive behavioural therapy. The concept of I-C spectrum pleads for less categorical and more dimensional approach that seems to be consistently adapted to clinical, genetic, pathophysiology and therapeutic realities.

Published
2014

20. [Switching and combining strategies of antidepressant medications]

Author

Thomas, Charpeaud, Fanny, Moliere, Maxime, Bubrovszky, Frédéric, Haesebaert, Najib, Allaïli, Rémy, Bation, Isabel, Nieto, Raphaëlle, Richieri, Ghassen, Saba, Frank, Bellivier, Djamila, Bennabi, Jérôme, Holtzmann, Vincent, Camus, Philippe, Courtet, Pierre, Courvoisier, Thierry, d'Amato, Olivier, Doumy, Marion, Garnier, Thierry, Bougerol, Christophe, Lançon, Emmanuel, Haffen, Marion, Leboyer, Pierre-Michel, Llorca, Guillaume, Vaiva, Wissam, El-Hage, and Bruno, Aouizerate

Subjects
Depressive Disorder, Drug Substitution, Practice Guidelines as Topic, Drug Resistance, Humans, Drug Interactions, Drug Therapy, Combination, Antidepressive Agents, Drug Administration Schedule
Abstract

Switching antidepressant medication may be helpful in depressed patients having no benefit from the initial antidepressant treatment. Before considering switching strategy, the initial antidepressant treatment should produce no therapeutic effect after at least 4 weeks of administration at adequate dosage. Choosing an antidepressant of pharmacologically distinct profile fails to consistently demonstrate a significant superiority in terms of effectiveness over the switching to another antidepressant within the same pharmacological class. Augmenting SSRI/SNRIs with mirtazapine/mianserin has become the most recommended strategy of antidepressant combinations. Augmenting SSRI with tricyclic drugs is now a less recommended strategy of antidepressant combinations given the increased risk for the occurrence of pharmacokinetic drug-drug interactions and adverse effects.

Published
2016

21. [Potentiation strategies]

Author

Olivier, Doumy, Djamila, Bennabi, Wissam, El-Hage, Najib, Allaïli, Rémy, Bation, Frank, Bellivier, Jérôme, Holtzmann, Maxime, Bubrovszky, Vincent, Camus, Thomas, Charpeaud, Pierre, Courvoisier, Thierry, d'Amato, Marion, Garnier, Frédéric, Haesebaert, Thierry, Bougerol, Christophe, Lançon, Fanny, Moliere, Isabel, Nieto, Raphaëlle, Richieri, Ghassen, Saba, Philippe, Courtet, Guillaume, Vaiva, Marion, Leboyer, Pierre-Michel, Llorca, Bruno, Aouizerate, and Emmanuel, Haffen

Subjects
Depressive Disorder, Thyroid Hormones, Bipolar Disorder, Drug Resistance, Thyrotropin, Drug Synergism, Antidepressive Agents, Treatment Outcome, Double-Blind Method, Lithium Carbonate, Meta-Analysis as Topic, Practice Guidelines as Topic, Humans, Anticonvulsants, Drug Therapy, Combination, Antipsychotic Agents, Randomized Controlled Trials as Topic
Abstract

Lithium is among the most classically recommended add-on therapeutic strategy for the management of depressive patients showing unsuccessful response to standard antidepressant medications. The effectiveness of the add-on strategy with lithium requires achieving plasma levels above 0.5 mEq/L. Mood-stabilizing antiepileptic drugs such as carbamazepine, valproate derivatives or lamotrigine have not demonstrated conclusive therapeutic effects for the management of depressive patients showing unsuccessful response to standard antidepressant medications. Thyroid hormones are considered among the currently recommended add-on therapeutic strategy for the management of depressive patients showing unsuccessful response to standard antidepressant medications. The effectiveness of the add-on strategy with thyroid hormones requires achieving plasma concentration of TSH close to the lower limits at the normal range (0.4 μUI/L) or even below it. Second-generation antipsychotics such as aripiprazole or quetiapine have consistently demonstrated significant therapeutic effects for the management of depressive patients showing unsuccessful response to standard antidepressant medications. Second-generation antipsychotics however require the careful monitoring of both cardiovascular and metabolic adverse effects.

Published
2016

22. Dépression résistante : les stratégies de potentialisation

Author

Frank Bellivier, Frédéric Haesebaert, Marion Garnier, Guillaume Vaiva, Raphaëlle Richieri, Vincent Camus, Christophe Lançon, Bruno Aouizerate, Thomas Charpeaud, Rémy Bation, Djamila Bennabi, Emmanuel Haffen, Fanny Moliere, Jérôme Holtzmann, Philippe Courtet, Maxime Bubrovszky, Wissam El-Hage, Thierry Bougerol, Ghassen Saba, Najib Allaïli, Marion Leboyer, Pierre-Michel Llorca, Isabel Nieto, Olivier Doumy, Pierre Courvoisier, Thierry d'Amato, Fondation FondaMental [Créteil], Centre hospitalier Charles Perrens [Bordeaux], Laboratoire de Neurosciences Intégratives et Cliniques - UFC (UR 481) (NEURO), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Clinique Psychiatrique Universitaire [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier le Vinatier [Bron], Variabilité de réponse aux Psychotropes (VariaPsy - U1144), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Pôle Psychiatrie et Neurologie [Grenoble], Centre Hospitalier Universitaire [Grenoble] (CHU), Service de Psychiatrie [CHRU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Hôpital Michel Fontan 1, UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), CHU Clermont-Ferrand, Département Universitaire de Psychiatrie - [Hôpital Sainte Marguerite - APHM] (Hôpitaux Sud), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Laboratoire de santé publique évaluation des systèmes de soins et santé perçue, INSERM U955, équipe 15, Service de psychiatrie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier-Réseau de coopération scientifique en santé mentale, Fondation FondaMental [Créteil]-Fondation FondaMental [Créteil]-Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), and Hôpital Charles Perrens

Subjects
medicine.medical_specialty, Lithium (medication), business.industry, Therapeutic effect, General Medicine, Carbamazepine, Pharmacology, Lamotrigine, 030227 psychiatry, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Antidepressant, Quetiapine, Aripiprazole, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Adverse effect, business, 030217 neurology & neurosurgery, ComputingMilieux_MISCELLANEOUS, medicine.drug
Abstract

Lithium is among the most classically recommended add-on therapeutic a strategy for the management of depressive patients showing unsuccessful a response to standard antidepressant medications. a The effectiveness of the add-on strategy with lithium requires achieving a plasma levels above 0.5 mEq/L. a Mood-stabilizing antiepileptic drugs such as carbamazepine, valproate a derivatives or lamotrigine have not demonstrated conclusive therapeutic a effects for the management of depressive patients showing unsuccessful a response to standard antidepressant medications. a Thyroid hormones are considered among the currently recommended add-on a therapeutic strategy for the management of depressive patients showing a unsuccessful response to standard antidepressant medications. a The effectiveness of the add-on strategy with thyroid hormones requires a achieving plasma concentration of TSH close to the lower limits at the a normal range (0.4 mUI/L) or even below it. Second-generation a antipsychotics such as aripiprazole or quetiapine have consistently a demonstrated significant therapeutic effects for the management of a depressive patients showing unsuccessful response to standard a antidepressant medications. a Second-generation antipsychotics however require the careful monitoring a of both cardiovascular and metabolic adverse effects.

Published
2016

23. [How to define treatment-resistant depression?]

Author

Jérôme, Holtzmann, Raphaëlle, Richieri, Ghassen, Saba, Najib, Allaïli, Rémy, Bation, Fanny, Moliere, Isabel, Nieto, Frank, Bellivier, Djamila, Bennabi, Maxime, Bubrovszky, Vincent, Camus, Thomas, Charpeaud, Pierre, Courvoisier, Frédéric, Haesebaert, Olivier, Doumy, Philippe, Courtet, Wissam, El-Hage, Marion, Garnier, Thierry, d'Amato, Christophe, Lançon, Marion, Leboyer, Pierre-Michel, Llorca, Guillaume, Vaiva, Thierry, Bougerol, Bruno, Aouizerate, Emmanuel, Haffen, Fondation FondaMental [Créteil], Pôle Psychiatrie et Neurologie [Grenoble], Centre Hospitalier Universitaire [Grenoble] (CHU), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Pôle de Psychiatrie [Hôpital Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital H. Mondor - A. Chenevier, Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier le Vinatier [Bron], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Service de Psychiatrie [CHRU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Hôpital Michel Fontan 1, Clinique Psychiatrique Universitaire [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), CHU Clermont-Ferrand, Hôpital Charles Perrens, Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)

Subjects
Depressive Disorder, Psychometrics, Drug Substitution, Mental Disorders, Drug Resistance, Avitaminosis, Comorbidity, Endocrine System Diseases, Antidepressive Agents, Diagnosis, Differential, Socioeconomic Factors, Recurrence, Quality of Life, Humans, Patient Compliance, Drug Interactions, Chronic Pain, Electroconvulsive Therapy, Stress, Psychological, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; The most largely used definition of the treatment-resistant depression relies on the failure of two successive trials of antidepressant treatment at an adequate dose and duration. The absence of response to previous antidepressant treatments should be assessed using specific and appropriate clinical instruments enabling a correct staging of the therapeutic resistance. A wide range of socio-demographic and clinical factors (i.e. psychiatric/somatic comorbidities) are classically associated with the therapeutic resistance. The aim of the treatment of major depression is to achieve a complete clinical remission. The presence of residual symptoms increases the risk for the subsequent occurrence of relapses and recurrences, hence facilitating the development of therapeutic resistance. The treatment-resistant depression has a deleterious impact on the social, familial or professional functioning, thereby leading to an impaired quality of life with serious socioeconomic consequences and costs.

Published
2016

24. Dépression résistante : les stratégies de changement et d’association de médicaments antidépresseurs

Author

Thierry d'Amato, Pierre-Michel Llorca, Najib Allaïli, Isabel Nieto, Frédéric Haesebaert, Jérôme Holtzmann, Ghassen Saba, Rémy Bation, Olivier Doumy, Guillaume Vaiva, Vincent Camus, Pierre Courvoisier, Christophe Lançon, Wissam El-Hage, Fanny Moliere, Maxime Bubrovszky, Thierry Bougerol, Frank Bellivier, Raphaëlle Richieri, Thomas Charpeaud, Bruno Aouizerate, Djamila Bennabi, Marion Leboyer, Emmanuel Haffen, Marion Garnier, Philippe Courtet, Fondation FondaMental [Créteil], CHU Clermont-Ferrand, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service de Psychiatrie [CHRU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Hôpital Michel Fontan 1, Centre Hospitalier le Vinatier [Bron], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire de santé publique évaluation des systèmes de soins et santé perçue, Département Universitaire de Psychiatrie - [Hôpital Sainte Marguerite - APHM] (Hôpitaux Sud), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), INSERM U955, équipe 15, Service de psychiatrie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier-Réseau de coopération scientifique en santé mentale, Fondation FondaMental [Créteil]-Fondation FondaMental [Créteil]-Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Variabilité de réponse aux Psychotropes (VariaPsy - U1144), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Neurosciences Intégratives et Cliniques - UFC (UR 481) (NEURO), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Pôle Psychiatrie et Neurologie [Grenoble], Centre Hospitalier Universitaire [Grenoble] (CHU), UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Hôpital Charles Perrens, and Centre hospitalier Charles Perrens [Bordeaux]

Subjects
chemistry.chemical_classification, business.industry, Therapeutic effect, Mirtazapine, General Medicine, Pharmacology, Mianserin, 3. Good health, 030227 psychiatry, 03 medical and health sciences, Antidepressant medication, 0302 clinical medicine, Increased risk, chemistry, medicine, Antidepressant, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], 030212 general & internal medicine, business, Depression (differential diagnoses), ComputingMilieux_MISCELLANEOUS, medicine.drug, Tricyclic
Abstract

Switching antidepressant medication may be helpful in depressed patients a having no benefit from the initial antidepressant treatment. a Before considering switching strategy, the initial antidepressant a treatment should produce no therapeutic effect after at least 4 weeks of a administration at adequate dosage. a Choosing an antidepressant of pharmacologically distinct profile fails a to consistently demonstrate a significant superiority in terms of a effectiveness over the switching to another antidepressant within the a same pharmacological class. a Augmenting SSRI/SNRIs with mirtazapine/mianserin has become the most a recommended strategy of antidepressant combinations. a Augmenting SSRI with tricyclic drugs is now a less recommended strategy a of antidepressant combinations given the increased risk for the a occurrence of pharmacokinetic drug-drug interactions and adverse a effects.

Published
2016

25. Toward a better characterisation and management of treatment-resistant depression in France through the network of expert centers (FondaMental)

Author

P. Courtet, Thierry Bougerol, Vincent Camus, Olivier Doumy, Raphaëlle Richieri, Thomas Charpeaud, Philippe Domenech, Marie-Noëlle Lefebvre, Wissam El-Hage, Isabel Nieto, C. Lançon, Laurent Schmitt, Frank Bellivier, Frédéric Haesebaert, Luc Mallet, Djamila Bennabi, J. Holtzmann, Antoine Yrondi, M. Leboyer, Florian Stephan, Marion Garnier, N. Alaīli, Emmanuel Haffen, C. Rabu, Thierry d'Amato, Michel Walter, Bruno Aouizerate, Fanny Moliere, Guillaume Vaiva, and P.-M. Llorca

Subjects
Pharmacology, Psychiatry and Mental health, Neurology, business.industry, Environmental resource management, medicine, Pharmacology (medical), Neurology (clinical), Medical emergency, business, medicine.disease, Treatment-resistant depression, Biological Psychiatry
Published
2017

26. Risk factors for treatment resistance in unipolar depression: a systematic review

Author

Frank Bellivier, Thierry Bougerol, P. Courtet, Bruno Aouizerate, Fanny Moliere, Pierre-Michel Llorca, Djamila Bennabi, Raphaëlle Richieri, Thomas Charpeaud, Vincent Camus, Christophe Lançon, Olivier Doumy, Wissam El-Hage, Thierry d'Amato, J. Holztmann, Ghassen Saba, M. Bubrovsky, Marion Leboyer, Isabel Nieto, Emmanuel Haffen, F. Haesbaert, Guillaume Vaiva, Fondation FondaMental [Créteil], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Pôle de Psychiatrie [Lille], PRES Université Lille Nord de France-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Departement de Psychiatrie, Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), Groupe d'étude des proliférations lymphoïdes (GPL), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux (NPsy-Sydo), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-CHU Clermont-Ferrand, Laboratoire de Neurosciences Intégratives et Cliniques - UFC (EA 481) (NEURO), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Clermont-Ferrand-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), and Laboratoire de Neurosciences Intégratives et Cliniques - UFC (UR 481) (NEURO)

Subjects
medicine.medical_specialty, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Medication Adherence, 03 medical and health sciences, Depressive Disorder, Treatment-Resistant, 0302 clinical medicine, Risk Factors, Medicine, Humans, In patient, Risk factor, Treatment resistance, Psychiatry, Depression (differential diagnoses), ComputingMilieux_MISCELLANEOUS, [SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, business.industry, [SCCO.NEUR]Cognitive science/Neuroscience, Mental Disorders, [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, medicine.disease, Antidepressive Agents, 3. Good health, 030227 psychiatry, Psychiatry and Mental health, Clinical Psychology, Mood disorders, Antidepressant, business, Psychosocial, Treatment-resistant depression, 030217 neurology & neurosurgery
Abstract

Background Treatment resistant depression is a complex disorder and an important source of morbidity and mortality. Identification of risk factors of resistance may be useful to improve early recognition as well as treatment selection and prediction of outcome in patients with depression. Methods The aim of this paper was to review the current status of knowledge regarding risk factors of treatment resistance in unipolar depression, in patients who failed to respond to at least two successive and adequate antidepressant treatments. Results Systematic literature search yielded 8 publications exploring clinical and biological factors. Specific psychiatric comorbidities, psychosocial factors, clinical characteristics of the depressive episode and biological markers emerge as possible risk factor for treatment resistant depression. Limitations Due to the lack of objective definition and diagnostic criteria for treatment resistant depression, and the paucity of reports on risk factors, our review only summarized a small number of studies. Conclusion Future investigations of risk factors should help to improve the understanding of the mechanisms underlying resistance in mood disorders and contribute to improve their therapeutic management.

Published
2014

28. [The OCD spectrum disorder revisited. Toward a bipolar impulsion-compulsion configuration]

Author

Olivier, Doumy and Bruno, Aouizerate

Subjects
Diagnosis, Differential, Obsessive-Compulsive Disorder, Impulsive Behavior, Compulsive Behavior, Humans, Comorbidity
Abstract

The so-called obsessive-compulsive spectrum disorder (OCD spectrum) is represented by a large variety of clinical entities. There are in general obsessive-compulsive disorder, trichotillomania or Gilles de la Tourette disease among the impulse control disorders, body dysmorphic disorder and hypochondriasis among the somatoform disorders. Updated overview of the OCD spectrum through a bipolar configuration with the impulsion-compulsion (I-C) spectrum, characterized by a failure to resist and control intrusive thoughts associated with repetitive behaviors that seem to be uncontrollable or require considerable efforts to suppress their execution. There are several disrupted processes in the I-C spectrum, including cognitive control, flexibility and behavioural inhibition. All these psychiatric affections demonstrated to share apparent similarities regarding clinical symptomatology, demographic considerations, comorbidity and course pattern, and responses to the serotonine reuptake inhibitors and cognitive behavioural therapy. The concept of I-C spectrum pleads for less categorical and more dimensional approach that seems to be consistently adapted to clinical, genetic, pathophysiology and therapeutic realities.

Published
2012

29. Is Deep Brain Stimulation Able to Make Antidepressants Effective in Resistant Obsessive-Compulsive Disorder?

Author

Abdelhamid Benazzouz, Olivier Doumy, Corinne Martin-Guehl, Bernard Bioulac, Alain Rougier, Michèle Allard, Pierre Burbaud, Bruno Aouizerate, Jean Tignol, Dominique Guehl, Jean-Yves Rotge, and Emmanuel Cuny

Subjects
Deep brain stimulation, Text mining, business.industry, Obsessive compulsive, medicine.medical_treatment, medicine, business, Neuroscience, Biological Psychiatry
Published
2012

30. Toward a new computer-based and easy-to-use tool for the objective measurement of motivational states in humans: a pilot study

Author

Catherine Semal, Camille Gouzien, Pierre Philip, Bruno Aouizerate, Daniela Cota, Laurent Demany, Olivier Doumy, and Pier Vincenzo Piazza

Subjects
media_common.quotation_subject, Psychological research, General Medicine, Stimulus (physiology), Test (assessment), Task (project management), Presentation, Functional neuroimaging, Perception, Psychophysics, Psychology, General Psychology, Cognitive psychology, media_common
Abstract

The experimental methods currently used for assessing motivational processes in humans have two major limitations. Some of them rely on global subjective assessments while others evaluate these processes using food-related tasks often coupled with functional neuroimaging techniques that have however limited availability and important associated costs. Here we propose a novel experimental computer-generated and easy-to-use tool primarily based on the presentation of food images and designed to provide a quantitative and objective measurement of motivational states in humans. Two tasks evaluating respectively visual and time discrimination capacities were developed and tested on a sample of 30 healthy subjects. The subjects were asked to compare a food stimulus (food picture in color) and its devalued counterpart (same image in grayscale), at each trial, assessing either the size (task A) or the duration of presentation (task B). Geometric figures presented in color or grayscale were used as controls. The subjects were invited to perform tasks A and B during three separate experimental sessions, one under fasting and two under satiety. Relative to their devalued counterparts, the food images were judged significantly greater in size and shorter in time of presentation in fasting than in satiety. In fasting, the size and the time of presentation for the food images were respectively estimated significantly greater and shorter than for the control images when compared to their respective devalued counterparts. Conversely, there was no overall change in the perception of size or duration of presentation for the control images between fasting and satiety conditions. Our findings support that hunger specifically affects the perception of visual food stimuli, and suggest that this novel computer-based test is potentially useful for the study of motivational states in human diseases that are characterized by serious disturbances in reward processing.

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31. Cognitive Behavioral Therapy for worry: a possible transdiagnostic approach?

Author

Bismuth, Sarah, Université de Bordeaux (UB), Olivier Doumy, and UB, Médecine

Subjects
Processus, [SDV] Life Sciences [q-bio], Thérapie cognitivo-comportementale, Souci, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Pensées répétitives, [SDV]Life Sciences [q-bio], Trouble anxieux généralisé, Trans diagnostique, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

Worry is a commonplace and ordinary repetitive thinking process. Depending on its intensity, it can be percieved as uncontrollable, interfere with one’s fonctionning, and so become pathological. It’s the case in the generalized anxiety disorder of whom it is the central symptom. At a time when, a dimensional view of mental disorders begin to emerge, worry as a repetitive negative thought, such as rumination, has been apprehended as a transdiagnostic process, found in several axis I disorders, and associated with the presence of negative affects. After a comparative presentation of different repetitive thoughts and a description of the main explicative models of worry, the aim of this review of litterature is to study the extent to which such an approach can be valid in cognitive and behavioral therapy, compared to the usual categorial view. Despite promissing studies, proofs concerning the efficacity of these complaint and process based therapy are insufficient, because of the few articles on the subject, as the main research concerns the generalized anxiety disorder. Furthermore, other approaches than cognitive and behavioural therapy can be interesting to target this process, such as mindfulness., Le souci est un phénomène cognitif de répétition de la pensée banal et habituel. Il peut selon son intensité être perçu comme incontrôlable, interférer avec le fonctionnement d'un individu et ainsi devenir pathologique. C'est le cas dans le trouble anxieux généralisé, dont il est le symptôme central. A l'heure où une approche dimensionnelle des pathologies mentales continue de questionner la vision catégorielle, le souci, en tant que pensée répétitive négative -au même titre que la rumination-, a été appréhendé comme un processus trans diagnostique, retrouvé dans de nombreuses pathologies de l'axe I, et associé à la présence d'affects négatifs. Après une présentation comparative des différentes pensées répétitives ainsi que des modèles du souci existant aujourd'hui, le but de cette revue de la littérature est d'étudier dans quelle mesure une telle approche peut être valide en thérapie cognitivo-comportementale, par rapport à l'approche catégorielle habituelle. Malgré des études prometteuses, les preuves concernant l'efficacité formelle de ces thérapies ciblées sur les processus et la plainte en comparaison à la prise en charge usuelle sont insuffisantes, de par le nombre peu important d'études sur le sujet, qui se focalisent davantage sur le trouble anxieux généralisé. Par ailleurs d'autres approches que la thérapie cognitivo-comportementale peuvent s'avérer intéressantes, comme la mindfulness notamment.

Published
2019

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