Olanzapine‐associated dose‐dependent alterations for weight and metabolic parameters in a prospective cohort

Metabolic abnormalities have been associated with olanzapine treatment. We assessed if olanzapine has dose-dependent effects on metabolic parameters with changes for weight, blood pressure, lipid and glucose profiles being modelled using linear mixed-effects models. The risk of metabolic abnormalities including early weight gain (EWG) (≥5% during first month) was assessed using mixed-effects logistic regression models. In 392 olanzapine-treated patients (median age 38.0 years, interquartile range [IQR] = 26.0-53.3, median dose 10.0 mg/day, IQR = 5.0-10.0 for a median follow-up duration of 40.0 days, IQR = 20.7-112.2), weight gain was not associated with olanzapine dose (p = 0.61) although it was larger for doses versus ≤10 mg/day (2.54 ± 5.55 vs. 1.61 ± 4.51% respectively, p = 0.01). Treatment duration and co-prescription of >2 antipsychotics, antidepressants, benzodiazepines and/or antihypertensive agents were associated with larger weight gain (p 10 mg/day were at higher EWG risk (odds risk: 2.15, 1.57-2.97). EWG might be prominent in high-dose olanzapine-treated patients with treatment duration and co-prescription of other medications being weight gain moderators. The lack of major dose-dependent patterns for weight gain emphasizes that olanzapine-treated patients are at weight gain risk regardless of the dose

Arbeitsmedizin

Das Kapitel ist in vier Unterkapital gegliedert. "Allgemeines zur Arbeitsmedizin" beinhaltet die Rolle und Ziele der Arbeitsmedizin und die wesentlichen gesetzlichen Grundlagen. "Berufskrankheiten" umfasst die Berufs- und Arbeitsplatzanamnese sowie die wichtigsten Berufskrankheiten und Noxen. Das dritte Unterkapitel behandelt die arbeitsassoziierten Gesundheitsstörungen, die Ergonomie, Arbeitsorganisation und Arbeitslosigkeit. Die Kapitel "Absenzen- und Case Management" sowie "Betriebliche Gesundheitsförderung und Arbeitsgestaltung" zeigen Möglichkeiten auf, wie ein Betrieb die Gesundheit und Arbeitsfähigkeit seiner Mitarbeiter aufrechterhalten und fördern kann. Das Kapitel befähigt die Studierenden, die Interaktion zwischen Arbeit und Gesundheit zu erkennen und adäquate Massnahmen zu ergreifen.[Autoren]]]> Occupational Medicine ; Occupational Diseases oai:serval.unil.ch:BIB_EFD9005BC107 2020-05-30T01:25:30Z phdthesis urnserval https://serval.unil.ch/notice/serval:BIB_EFD9005BC107 Résultats à court terme des arthroplasties totales de hanche non cimentées chez des patients de moins de 60 ans Larequi, Ivan-Philippe Université de Lausanne, Faculté de médecine info:eu-repo/semantics/doctoralThesis phdthesis 1999 fre https://serval.unil.ch/resource/serval:BIB_EFD9005BC107.P001/REF.pdf http://nbn-resolving.org/urn/resolver.pl?urn=urn:nbn:ch:serval-BIB_EFD9005BC1073 info:eu-repo/semantics/altIdentifier/urn/urn:nbn:ch:serval-BIB_EFD9005BC1073 info:eu-repo/semantics/restrictedAccess Restricted: indefinite embargo Copying allowed only for non-profit organizations https://serval.unil.ch/disclaimer application/pdf oai:serval.unil.ch:BIB_EFD90D5BB70B 2020-05-30T01:25:30Z openaire documents urnserval https://serval.unil.ch/notice/serval:BIB_EFD90D5BB70B Association Between Plasma Caffeine and Other Methylxanthines and Metabolic Parameters in a Psychiatric Population Treated With Psychotropic Drugs Inducing Metabolic Disturbances info:doi:10.3389/fpsyt.2018.00573 info:eu-repo/semantics/altIdentifier/doi/10.3389/fpsyt.2018.00573 info:eu-repo/semantics/altIdentifier/pmid/30473668 Delacrétaz, Aurélie Vandenberghe, Frederik Glatard, Anaïs Levier, Axel Dubath, Céline Ansermot, Nicolas Crettol, Séverine Gholam-Rezaee, Mehdi Guessous, Idris Bochud, Murielle von Gunten, Armin Conus, Philippe Eap, Chin B. info:eu-repo/semantics/article article 2018-11-09 Frontiers in Psychiatry, vol. 9 info:eu-repo/semantics/altIdentifier/pissn/1664-0640 <![CDATA[Importance: Multiple studies conducted in the general population identified an association between self-reported coffee consumption and plasma lipid levels. To date, no study assessed whether and which plasma methylxanthines (caffeine and/or its metabolites, i.e., paraxanthine, theophylline, and theobromine) are associated with plasma lipids. In psychiatric patients, an important coffee consumption is often reported and many psychotropic drugs can induce a rapid and substantial increase of plasma lipid levels. Objective: To determine whether plasma methylxanthines are associated with metabolic parameters in psychiatric patients receiving treatments known to induce metabolic disturbances. Design, Setting, and Participants: Data were obtained from a prospective study including 630 patients with metabolic parameters [i.e., body mass index (BMI), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), and fasting triglycerides (TG)] monitored routinely during psychotropic treatment. Exposures: Plasma methylxanthines levels. Main Outcomes and Measures: Metabolic variables including BMI and plasma lipid levels. Results: Multivariate analyses indicated that BMI, TC, HDL-C, and non-HDL-C increased significantly with increasing total methylxanthines (pcorrected &lt;= 0.05). In addition, compared to patients with plasma caffeine concentration in the lowest quartile, those with caffeine concentration in the highest quartile were twice more prone to suffer from non-HDL hypercholesterolemia (p(corrected) = 0.05), five times more likely to suffer from hypertriglyceridemia (p(corrected) = 0.01) and four times more susceptible to be overweight (p(corrected) = 0.01). Conclusions and Relevance: This study showed that plasma caffeine and other methylxanthines are associated with worsening of metabolic parameters in patients receiving psychotropic treatments known to induce metabolic disturbances. It emphasizes that important caffeine consumption could be considered as an additional environmental risk factor for metabolic worsening in patients receiving such treatments

Association Between Plasma Caffeine and Other Methylxanthines and Metabolic Parameters in a Psychiatric Population Treated With Psychotropic Drugs Inducing Metabolic Disturbances

Importance: Multiple studies conducted in the general population identified an association between self-reported coffee consumption and plasma lipid levels. To date, no study assessed whether and which plasma methylxanthines (caffeine and/or its metabolites, i.e., paraxanthine, theophylline, and theobromine) are associated with plasma lipids. In psychiatric patients, an important coffee consumption is often reported and many psychotropic drugs can induce a rapid and substantial increase of plasma lipid levels.Objective: To determine whether plasma methylxanthines are associated with metabolic parameters in psychiatric patients receiving treatments known to induce metabolic disturbances.Design, Setting, and Participants: Data were obtained from a prospective study including 630 patients with metabolic parameters [i.e., body mass index (BMI), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), and fasting triglycerides (TG)] monitored routinely during psychotropic treatment.Exposures: Plasma methylxanthines levels.Main Outcomes and Measures: Metabolic variables including BMI and plasma lipid levels.Results: Multivariate analyses indicated that BMI, TC, HDL-C, and non-HDL-C increased significantly with increasing total methylxanthines (pcorrected ≤ 0.05). In addition, compared to patients with plasma caffeine concentration in the lowest quartile, those with caffeine concentration in the highest quartile were twice more prone to suffer from non-HDL hypercholesterolemia (pcorrected = 0.05), five times more likely to suffer from hypertriglyceridemia (pcorrected = 0.01) and four times more susceptible to be overweight (pcorrected = 0.01).Conclusions and Relevance: This study showed that plasma caffeine and other methylxanthines are associated with worsening of metabolic parameters in patients receiving psychotropic treatments known to induce metabolic disturbances. It emphasizes that important caffeine consumption could be considered as an additional environmental risk factor for metabolic worsening in patients receiving such treatments

Clinical, environmental and epigenetic moderators of cardiometabolic adverse effects in patients receiving psychotropic treatments

Psychiatric patients display an important prevalence of cardiometabolic disturbances, increasing their risk of developing and dying from cardiovascular diseases. This concerning situation results from a combination of genetic and environmental factors. Besides, the medications indicated to treat mental illnesses, including most antipsychotics, many mood stabilizers and some antidepressants, induce weight gain and metabolic alterations. The aim of the present thesis was to assess the metabolic health of a Swiss psychiatric cohort and to explore clinical, environmental and epigenetic risk factors to improve knowledge of psychotropic drugs’ metabolic effects. In the first study, the probabilities of cardiovascular events and death were estimated in a sample of psychiatric patients and a sample of the general population, revealing a similar level of risk. However, metabolic syndrome prevalence was much higher in the psychiatric cohort, especially in younger individuals (&lt;50 years) and in women. In the second project, the association between socioeconomic status and changes in cardiometabolic parameters was evaluated over one year after the prescription of a psychotropic medication at risk for weight gain. Patients with low compared to high socioeconomic status were three times more likely to develop metabolic syndrome. Validating these observations, educational attainment, a marker of socioeconomic status, was found to be causally related to body mass index in an independent cohort of individuals receiving psychotropic treatments. The last study focused on quetiapine, an atypical antipsychotic, and was able to show that its metabolic adverse reactions depended on the daily dosage. Patients on lower doses developed indeed less side effects. However, the magnitude of this effect was small, and low doses of quetiapine still carried a non-negligible risk. Eventually, preliminary results from an ongoing project have revealed a global increase in DNA methylation levels following psychotropic treatment initiation and suggested that some site-specific modifications may play a role in drug-induced metabolic side effects. These findings are critical in raising awareness of the poor metabolic health highly prevalent in psychiatry. They provide more insights into the risk factors for metabolic adverse reactions, which can be directly used in clinical practice to benefit care. The results of ongoing studies will provide a better understanding of the mechanisms leading to these adverse events, hopefully enabling development of new strategies to prevent their occurrence, to help identify at risk patients and to guide prescription choices. -- Les patients psychiatriques présentent une prévalence importante de troubles cardiométaboliques, ce qui augmente leur risque de développer des maladies cardiovasculaires et d’en décéder. Cette situation préoccupante résulte d’une combinaison de facteurs génétiques et environnementaux. Par ailleurs, les médicaments pour traiter les maladies mentales, dont la plupart des neuroleptiques, plusieurs stabilisateurs de l’humeur et certains antidépresseurs, induisent une prise de poids et des perturbations métaboliques. L'objectif de la présente thèse était d'évaluer la santé métabolique d'une cohorte psychiatrique suisse et d'explorer les facteurs de risque cliniques, environnementaux et épigénétiques afin d’améliorer les connaissances sur les effets métaboliques des psychotropes. Dans la première étude, les probabilités d'événements et de décès cardiovasculaires ont été estimées dans un échantillon de patients psychiatriques et de population générale, indiquant un niveau de risque similaire. Cependant, la prévalence de syndrome métabolique dans la cohorte psychiatrique était largement supérieure, en particulier chez les jeunes (&lt;50 ans) et les femmes. Dans le second projet, l'association entre le statut socio-économique et les changements des paramètres cardiométaboliques a été évaluée sur une période d'un an après la prescription d'un traitement psychotrope à risque de prise de poids. Les patients ayant un statut faible étaient trois fois plus susceptibles de développer un syndrome métabolique que ceux ayant un statut élevé. Validant ces résultats, un lien de cause à effet entre le niveau d'éducation, un marqueur du profil socio-économique, et l'indice de masse corporelle a pu être mis en évidence dans une cohorte indépendante recevant des psychotropes. La dernière étude s'est concentrée sur la quétiapine, un neuroleptique atypique, et a pu montrer que ses effets indésirables métaboliques dépendaient de la dose quotidienne. Les patients prenant des doses plus faibles développaient en effet moins d’effets secondaires. Toutefois, l'ampleur de cet effet était modeste, et les petites doses comportaient tout de même un risque non négligeable. Enfin, les résultats préliminaires d'un projet en cours ont révélé une augmentation globale du niveau de méthylation de l’ADN à la suite d’un traitement psychotrope et suggèrent que certaines modifications spécifiques pourraient contribuer à l’apparition des effets secondaires métaboliques. Ces résultats sont essentiels pour faire prendre conscience de la mauvaise santé métabolique des patients psychiatriques. Ils fournissent davantage d'informations sur les facteurs de risque des effets secondaires métaboliques, qui peuvent être directement utilisées en pratique clinique au bénéfice des soins. Les résultats des études en cours permettront de mieux comprendre les mécanismes conduisant à ces effets indésirables, de développer de nouvelles stratégies pour les prévenir, d’aider à identifier les patients à risque et d’orienter les choix de prescription. -- Les patients souffrant de maladies mentales, incluant la schizophrénie, les troubles bipolaires et la dépression majeure, ont une espérance de vie réduite par rapport à la population générale. Ces patients ont un plus grand risque de développer des maladies cardiovasculaires en raison de leur patrimoine génétique et de facteurs liés au style de vie, ce qui explique en partie le taux de mortalité élevé. Par ailleurs, les médicaments qui leur sont prescrits, dont la plupart des neuroleptiques, plusieurs stabilisateurs de l’humeur et certains antidépresseurs, favorisent la prise de poids et l’apparition d’un syndrome métabolique. L'objectif de cette thèse était d'évaluer l’état de santé cardiovasculaire d’une cohorte psychiatrique et d'explorer les facteurs de risque conduisant aux effets secondaires métaboliques des psychotropes. Tout d’abord, des outils ont été utilisés pour prédire l’arrivée d’événements et de décès cardiovasculaires sur 10 ans, révélant un risque similaire entre patients psychiatriques et population générale. Cependant, la prévalence d’un syndrome métabolique était beaucoup plus importante dans la cohorte psychiatrique, surtout chez les jeunes (&lt;50 ans) et les femmes. Dans un second projet, l’impact du statut socio-économique sur les changements des paramètres cardiométaboliques a été évalué sur une période d'un an après la prescription d'un traitement psychotrope à risque de prise de poids. Il a notamment été prouvé que les patients ayant un statut faible étaient trois fois plus susceptibles de développer un syndrome métabolique que ceux ayant un statut élevé. La dernière étude s'est concentrée sur la quétiapine, un neuroleptique largement utilisé en psychiatrie, et a pu montrer que ses effets métaboliques dépendaient de la dose journalière. Enfin, les résultats préliminaires d'un projet impliquant la génétique ont indiqué que les médicaments psychotropes pourraient induire des dérèglements du métabolisme en modifiant l’expression des gènes. Ces résultats sont essentiels pour faire prendre conscience de la mauvaise santé métabolique des patients psychiatriques. Ils fournissent des informations sur les facteurs de risque menant aux effets indésirables métaboliques, qui peuvent être directement utiles en clinique. Les résultats des études en cours permettront de mieux comprendre les mécanismes conduisant à ces effets secondaires, de développer de nouvelles stratégies pour les prévenir, d’aider à identifier les patients à risque et d’orienter les choix de prescription

DNA methylation may partly explain psychotropic drug-induced metabolic side effects: results from a prospective 1-month observational study

Abstract Background Metabolic side effects of psychotropic medications are a major drawback to patients’ successful treatment. Using an epigenome-wide approach, we aimed to investigate DNA methylation changes occurring secondary to psychotropic treatment and evaluate associations between 1-month metabolic changes and both baseline and 1-month changes in DNA methylation levels. Seventy-nine patients starting a weight gain inducing psychotropic treatment were selected from the PsyMetab study cohort. Epigenome-wide DNA methylation was measured at baseline and after 1 month of treatment, using the Illumina Methylation EPIC BeadChip. Results A global methylation increase was noted after the first month of treatment, which was more pronounced (p < 2.2 × 10–16) in patients whose weight remained stable (< 2.5% weight increase). Epigenome-wide significant methylation changes (p < 9 × 10−8) were observed at 52 loci in the whole cohort. When restricting the analysis to patients who underwent important early weight gain (≥ 5% weight increase), one locus (cg12209987) showed a significant increase in methylation levels (p = 3.8 × 10–8), which was also associated with increased weight gain in the whole cohort (p = 0.004). Epigenome-wide association analyses failed to identify a significant link between metabolic changes and methylation data. Nevertheless, among the strongest associations, a potential causal effect of the baseline methylation level of cg11622362 on glycemia was revealed by a two-sample Mendelian randomization analysis (n = 3841 for instrument-exposure association; n = 314,916 for instrument-outcome association). Conclusion These findings provide new insights into the mechanisms of psychotropic drug-induced weight gain, revealing important epigenetic alterations upon treatment, some of which may play a mediatory role

Additional file 1 of DNA methylation may partly explain psychotropic drug-induced metabolic side effects: results from a prospective 1-month observational study

Additional file 1. Appendix: Supplementary Methods and Results. Supplementary figures and tables