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1. Self-reported caffeine consumption miss-matched consumption measured by plasma levels of caffeine and its metabolites: results from two population-based studies

Author

Laaboub, Nermine, Ranjbar, Setareh, Strippoli, Marie-Pierre F., Marques-Vidal, Pedro, Estoppey-Younes, Sandrine, Ponte, Belen, Pruijm, Menno, Vogt, Bruno, Ansermot, Nicolas, Crettol, Séverine, Vandenberghe, Frederik, Vollenweider, Peter, Preisig, Martin, Bochud, Murielle, and EAP, Chin B.

Published
2024
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5. Exploring low clozapine C/D ratios, inverted clozapine-norclozapine ratios and undetectable concentrations as measures of non-adherence in clozapine patients: A literature review and a case series of 17 patients from 3 studies

Author

Ruan, Can-Jun, Olmos, Ismael, Ricciardi, Carina, Schoretsanitis, Georgios, Vincent, Philippe D., Anıl Yağcıoğlu, A. Elif, Eap, Chin B., Baptista, Trino, Clark, Scott R., Fernandez-Egea, Emilio, Kim, Se Hyun, Lane, Hsien-Yuan, Leung, Jonathan, Maroñas Amigo, Olalla, Motuca, Mariano, Every-Palmer, Susanna, Procyshyn, Ric M., Rohde, Christopher, Suhas, Satish, Schulte, Peter F.J., Spina, Edoardo, Takeuchi, Hiroyoshi, Verdoux, Hélène, Correll, Christoph U., Molden, Espen, De Las Cuevas, Carlos, and de Leon, Jose

Published
2024
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6. Clozapine ultrarapid metabolism during weak induction probably exists but requires careful diagnosis. A literature review, five new cases and a proposed definition

Author

Schoretsanitis, Georgios, Anıl Yağcıoğlu, A. Elif, Ruan, Can-Jun, Eap, Chin B., Molden, Espen, Baptista, Trino, Clark, Scott R., Fernandez-Egea, Emilio, Kim, Se Hyun, Lane, Hsien-Yuan, Leung, Jonathan, Maroñas Amigo, Olalla, Motuca, Mariano, Olmos, Ismael, Every-Palmer, Susanna, Procyshyn, Ric M., Rohde, Christopher, Satish, Suhas, Schulte, Peter F.J., Spina, Edoardo, Takeuchi, Hiroyoshi, Verdoux, Hélène, Correll, Christoph U., and de Leon, Jose

Published
2024
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9. Guía internacional para una dosificación más segura de la clozapina en adultos mediante el uso de 6 titulaciones personalizadas de dosis basados en la etnicidad, la proteína C reactiva y los niveles de clozapina

Author

de Leon, Jose, Schoretsanitis, Georgios, Smith, Robert L., Molden, Espen, Solismaa, Anssi, Seppälä, Niko, Kopeček, Miloslav, Švancer, Patrik, Olmos, Ismael, Ricciardi, Carina, Iglesias-Garcia, Celso, Iglesias-Alonso, Ana, Spina, Edoardo, Ruan, Can-Jun, Wang, Chuan-Yue, Wang, Gang, Tang, Yi-Lang, Lin, Shih-Ku, Lane, Hsien-Yuan, Kim, Yong Sik, Kim, Se Hyun, Rajkumar, Anto P., González-Esquivel, Dinora F., Jung-Cook, Helgi, Baptista, Trino, Rohde, Christopher, Nielsen, Jimmi, Verdoux, Hélène, Quiles, Clelia, Sanz, Emilio J., De las Cuevas, Carlos, Cohen, Dan, Schulte, Peter F.J., Ertuğrul, Aygün, Anıl Yağcıoğlu, A. Elif, Chopra, Nitin, McCollum, Betsy, Shelton, Charles, Cotes, Robert O., Kaithi, Arun R., Kane, John M., Farooq, Saeed, Ng, Chee H., Bilbily, John, Hiemke, Christoph, López-Jaramillo, Carlos, McGrane, Ian, Lana, Fernando, Eap, Chin B., Arrojo-Romero, Manuel, Rădulescu, Flavian Ştefan, Seifritz, Erich, Every-Palmer, Susanna, Bousman, Chad A., Bebawi, Emmanuel, Bhattacharya, Rahul, Kelly, Deanna L., Otsuka, Yuji, Lazary, Judit, Torres, Rafael, Yecora, Agustin, Motuca, Mariano, Chan, Sherry Kit Wa, Zolezzi, Monica, Ouanes, Sami, De Berardis, Domenico, Grover, Sandeep, Procyshyn, Ric M., Adebayo, Richard A., Kirilochev, Oleg O., Soloviev, Andrey, Fountoulakis, Konstantinos N., Wilkowska, Alina, Cubała, Wiesław Jerzy, Ayub, Muhammad, Silva, Alzira, Bonelli, Raphael M., Villagrán-Moreno, José María, Crespo-Facorro, Benedicto, Temmingh, Henk, Decloedt, Eric, Pedro, Maria Rosel, Takeuchi, Hiroyoshi, Tsukahara, Masaru, Gründer, Gerhard, Sagud, Marina, Celofiga, Andreja, Ignjatovic Ristic, Dragana, Ortiz, Bruno Bertolucci, Elkis, Helio, Pacheco Palha, António José, Llerena, Adrián, Fernandez-Egea, Emilio, Siskind, Dan, Weizman, Abraham, Masmoudi, Rim, Mohd Saffian, Shamin, Leung, Jonathan G., Buckley, Peter F., Marder, Stephen R., Citrome, Leslie, Freudenreich, Oliver, Correll, Christoph U., and Müller, Daniel J.

Published
2023
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10. Therapeutic Drug Monitoring of Olanzapine: Effects of Clinical Factors on Plasma Concentrations in Psychiatric Patients

Author

Ansermot, Nicolas, primary, Vathanarasa, Harish, additional, Ranjbar, Setareh, additional, Gholam, Mehdi, additional, Crettol, Séverine, additional, Vandenberghe, Frederik, additional, Gamma, Franziska, additional, Plessen, Kerstin Jessica, additional, von Gunten, Armin, additional, Conus, Philippe, additional, and Eap, Chin B., additional

Published
2024
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11. Clinical predictors of antipsychotic treatment resistance: Development and internal validation of a prognostic prediction model by the STRATA-G consortium

Author

Smart, Sophie E., Agbedjro, Deborah, Pardiñas, Antonio F., Ajnakina, Olesya, Alameda, Luis, Andreassen, Ole A., Barnes, Thomas R.E., Berardi, Domenico, Camporesi, Sara, Cleusix, Martine, Conus, Philippe, Crespo-Facorro, Benedicto, D'Andrea, Giuseppe, Demjaha, Arsime, Di Forti, Marta, Do, Kim, Doody, Gillian, Eap, Chin B., Ferchiou, Aziz, Guidi, Lorenzo, Homman, Lina, Jenni, Raoul, Joyce, Eileen, Kassoumeri, Laura, Lastrina, Ornella, Melle, Ingrid, Morgan, Craig, O'Neill, Francis A., Pignon, Baptiste, Restellini, Romeo, Richard, Jean-Romain, Simonsen, Carmen, Španiel, Filip, Szöke, Andrei, Tarricone, Ilaria, Tortelli, Andrea, Üçok, Alp, Vázquez-Bourgon, Javier, Murray, Robin M., Walters, James T.R., Stahl, Daniel, and MacCabe, James H.

Published
2022
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12. Publisher Correction: Insomnia disorders are associated with increased cardiometabolic disturbances and death risks from cardiovascular diseases in psychiatric patients treated with weight-gain-inducing psychotropic drugs: results from a Swiss cohort

Author

Laaboub, Nermine, Dubath, Céline, Ranjbar, Setareh, Sibailly, Guibet, Grosu, Claire, Piras, Marianna, Délessert, Didier, Richard-Lepouriel, Hélène, Ansermot, Nicolas, Crettol, Severine, Vandenberghe, Frederik, Grandjean, Carole, Delacrétaz, Aurélie, Gamma, Franziska, Plessen, Kerstin Jessica, von Gunten, Armin, Conus, Philippe, and Eap, Chin B.

Published
2022
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13. Insomnia disorders are associated with increased cardiometabolic disturbances and death risks from cardiovascular diseases in psychiatric patients treated with weight-gain-inducing psychotropic drugs: results from a Swiss cohort

Author

Laaboub, Nermine, Dubath, Céline, Ranjbar, Setareh, Sibailly, Guibet, Grosu, Claire, Piras, Marianna, Délessert, Didier, Richard-Lepouriel, Hélène, Ansermot, Nicolas, Crettol, Severine, Vandenberghe, Frederik, Grandjean, Carole, Delacrétaz, Aurélie, Gamma, Franziska, Plessen, Kerstin Jessica, von Gunten, Armin, Conus, Philippe, and Eap, Chin B.

Published
2022
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15. Pharmacokinetics and Pharmacodynamics of Inhaled Nicotine Salt and Free-Base Using an E-cigarette: A Randomized Crossover Study.

Author

Christen, Samuel E, Hermann, Laura, Bekka, Elias, Vonwyl, Celina, Hammann, Felix, van der Velpen, Vera, Eap, Chin B, Benowitz, Neal L, Haschke, Manuel, and Liakoni, Evangelia

Subjects
COTININE, ELECTRONIC cigarettes, NICOTINE, SMOKING, SMOKING cessation
Abstract

Introduction Popular "pod-style" e-cigarettes commonly use nicotine salt-based e-liquids that cause less irritation when inhaled and can deliver higher nicotine concentrations than free-base nicotine. This study investigated the pharmacokinetic and pharmacodynamic effects of different nicotine formulations (salt vs. free-base) and concentrations that might influence systemic nicotine absorption and appeal of e-cigarettes. Aims and Methods In this randomized, double-blind, within-subject crossover study, 20 non-nicotine-naïve participants were switched among three e-liquids (free-base nicotine 20 mg/mL, nicotine salt 20 mg/mL, nicotine salt 40 mg/mL) using a refillable pod system and a standardized vaping protocol (one puff every 30 seconds, 10 puffs total). Serum nicotine concentrations and vital signs were assessed over 180 minutes; direct effects, craving, satisfaction, withdrawal, and respiratory symptoms were measured using questionnaires. CYP2A6 genotypes and the nicotine metabolite ratio were also assessed. Results Eleven (55%) participants were male and the median age was 23.5 years (range 18–67). All three formulations differed significantly in peak serum nicotine concentration (baseline adjusted Cmax, median (range): 12.0 ng/mL (1.6–27.3), 5.4 ng/mL (1.9–18.7), and 3.0 ng/mL (1.3–8.8) for nicotine salt 40 mg/mL, nicotine salt 20 mg/mL and free-base 20 mg/mL, respectively). All groups reached Cmax 2.0–2.5 minutes (median) after their last puff. Differences in subjective effects were not statistically significant. No serious adverse events were observed. Conclusions Free-base 20 mg/mL formulations achieved lower blood nicotine concentrations than nicotine salt 20 mg/mL, while 40 mg/mL nicotine salt yielded concentrations similar to cigarette smoking. The findings can inform regulatory policy regarding e-liquids and their potential use in smoking cessation. Implications Nicotine salt formulations inhaled by an e-cigarette led to higher nicotine delivery compared to nicotine-free-base formulations with the same nicotine concentration. These findings should be considered in future regulatory discussions. The 40 mg/mL nicotine salt formulation showed similar nicotine delivery as combustible cigarettes, albeit at concentrations over the maximum limit for e-liquids allowed in the European Union. Nicotine delivery resembling combustible cigarettes might be beneficial for smokers willing to quit to adequately alleviate withdrawal symptoms. However, increased nicotine delivery can also pose a public health risk, raising concerns about abuse liability, especially among youth and nonsmokers. [ABSTRACT FROM AUTHOR]

Published
2024
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17. Metabolic disturbances are risk factors for readmission to psychiatric hospitals in non-smokers but not in smokers: results from a Swiss psychiatric cohort and in first-episode psychosis patients

Author

Laaboub, Nermine, primary, Locatelli, Isabella, additional, Grosu, Claire, additional, Piras, Marianna, additional, Ngoc, Tram Ho, additional, Ranjbar, Setareh, additional, Preisig, Martin, additional, Elowe, Julien, additional, von Gunten, Armin, additional, Conus, Philippe, additional, and Eap, Chin B., additional

Published
2024
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19. Correction: Socio-economic position as a moderator of cardiometabolic outcomes in patients receiving psychotropic treatment associated with weight gain: results from a prospective 12-month inception cohort study and a large population-based cohort

Author

Dubath, Céline, Gholam-Rezaee, Mehdi, Sjaarda, Jennifer, Levier, Axel, Saigi-Morgui, Nuria, Delacrétaz, Aurélie, Glatard, Anaïs, Panczak, Radoslaw, Correll, Christoph U., Solida, Alessandra, Plessen, Kerstin Jessica, von Gunten, Armin, Kutalik, Zoltan, Conus, Philippe, and Eap, Chin B.

Published
2021
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22. Genetic immune and inflammatory markers associated with diabetes in solid organ transplant recipients

Author

Quteineh, Lina, Wójtowicz, Agnieszka, Bochud, Pierre-Yves, Crettol, Severine, Vandenberghe, Frederik, Venetz, Jean-Pierre, Manuel, Oriol, Golshayan, Dela, Lehmann, Roger, Mueller, Nicolas J., Binet, Isabelle, van Delden, Christian, Steiger, Jürg, Mohacsi, Paul, Dufour, Jean-Francois, Soccal, Paola M., Kutalik, Zoltan, Marques-Vidal, Pedro, Vollenweider, Peter, Recher, Mike, Hess, Christoph, Pascual, Manuel, and Eap, Chin B.

Published
2019
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23. Early changes of blood lipid levels during psychotropic drug treatment as predictors of long-term lipid changes and of new onset dyslipidemia

Author

Delacrétaz, Aurélie, Vandenberghe, Frederik, Gholam-Rezaee, Mehdi, Saigi Morgui, Nuria, Glatard, Anaïs, Thonney, Jacques, Solida-Tozzi, Alessandra, Kolly, Stéphane, Gallo, Sylfa Fassassi, Baumann, Philipp, Berney, Sylvie, Zulauff, Sandrine Valloton, Aubry, Jean-Michel, Hasler, Roland, Ebbing, Karsten, von Gunten, Armin, Conus, Philippe, and Eap, Chin B.

Published
2018
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26. Clozapine ultrarapid metabolism during weak induction probably exists but requires careful diagnosis. A literature review, five new cases and a proposed definition

Author

Schoretsanitis, Georgios, primary, Anıl Yağcıoğlu, A. Elif, additional, Ruan, Can-Jun, additional, Eap, Chin B., additional, Molden, Espen, additional, Baptista, Trino, additional, Clark, Scott R., additional, Fernandez-Egea, Emilio, additional, Kim, Se Hyun, additional, Lane, Hsien-Yuan, additional, Leung, Jonathan, additional, Maroñas Amigo, Olalla, additional, Motuca, Mariano, additional, Olmos, Ismael, additional, Every-Palmer, Susanna, additional, Procyshyn, Ric M., additional, Rohde, Christopher, additional, Satish, Suhas, additional, Schulte, Peter F.J., additional, Spina, Edoardo, additional, Takeuchi, Hiroyoshi, additional, Verdoux, Hélène, additional, Correll, Christoph U., additional, and de Leon, Jose, additional

Published
2023
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28. Infant exposure to Fluvoxamine through placenta and human milk: a case series - A contribution from the ConcePTION project

Author

Monfort, Anaëlle, primary, Cardoso, Evelina, additional, Eap, Chin B., additional, Fischer Fumeaux, Céline J., additional, Graz, Myriam Bickle, additional, Morisod Harari, Mathilde, additional, Weisskopf, Etienne, additional, Gandia, Peggy, additional, Allegaert, Karel, additional, Nordeng, Hedvig, additional, Hascoët, Jean-Michel, additional, Claris, Olivier, additional, Epiney, Manuella, additional, Csajka, Chantal, additional, Guidi, Monia, additional, Ferreira, Ema, additional, and Panchaud, Alice, additional

Published
2023
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29. Infant exposure to Fluvoxamine through placenta and human milk:a case series - A contribution from the ConcePTION project

Author

Monfort, Anaëlle, Cardoso, Evelina, Eap, Chin B., Fischer Fumeaux, Céline J., Graz, Myriam Bickle, Morisod Harari, Mathilde, Weisskopf, Etienne, Gandia, Peggy, Allegaert, Karel, Nordeng, Hedvig, Hascoët, Jean Michel, Claris, Olivier, Epiney, Manuella, Csajka, Chantal, Guidi, Monia, Ferreira, Ema, Panchaud, Alice, Monfort, Anaëlle, Cardoso, Evelina, Eap, Chin B., Fischer Fumeaux, Céline J., Graz, Myriam Bickle, Morisod Harari, Mathilde, Weisskopf, Etienne, Gandia, Peggy, Allegaert, Karel, Nordeng, Hedvig, Hascoët, Jean Michel, Claris, Olivier, Epiney, Manuella, Csajka, Chantal, Guidi, Monia, Ferreira, Ema, and Panchaud, Alice

Abstract

Introduction: Fluvoxamine is widely used to treat depression during pregnancy and lactation. However, limited data are available on its transfer to the fetus or in human milk. This case series provides additional information on the infant exposure to fluvoxamine during pregnancy and lactation. Case presentation: Two women, aged 38 and 34 years, diagnosed with depression were treated with 50 mg fluvoxamine during pregnancy and lactation. At delivery a paired maternal and cord blood sample was collected for each woman. The first mother exclusively breastfed her child for 4 months and gave one foremilk and one hindmilk sample at 2 days and 4 weeks post-partum, whereas the second mother did not breastfeed. Results: The cord to plasma concentration ratios were 0.62 and 0.48, respectively. At 2 weeks post-partum, relative infant doses (RID) were 0.47 and 0.57% based on fluvoxamine concentrations in foremilk and hindmilk, respectively. At 4 weeks post-partum, the RIDs were 0.35 and 0.90%, respectively. The child from the first mother was born healthy and showed a normal development at the 6th, 18th and 36th month follow-ups. One of the twins from the second woman was hospitalized for hypoglycemia that was attributed to gestational diabetes and low birth weight. The second one was born healthy. Conclusion: These results suggest a minimal exposure to fluvoxamine during lactation which is in accordance with previously published data. Larger clinical and pharmacokinetic studies assessing the long-term safety of this drug during lactation and the variability of its exposure through breastmilk are warranted.

Published
2023

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

Author

Schoretsanitis, Georgios, Dubath, Céline, Grosu, Claire, Piras, Marianna, Laaboub, Nermine, Ranjbar, Setareh, Ansermot, Nicolas, Crettol, Séverine, Vandenberghe, Frederik, Gamma, Franziska, von Gunten, Armin, Plessen, Kerstin Jessica, Seifritz, Erich, Conus, Philippe, Eap, Chin B, University of Zurich, and Schoretsanitis, Georgios

Subjects
Adult, Pharmacology, 3005 Toxicology, 610 Medicine & health, General Medicine, Weight Gain, Toxicology, Benzodiazepines, antipsychotic, metabolic syndrome, obesity, olanzapine, weight gain, 3004 Pharmacology, Olanzapine, 10054 Clinic for Psychiatry, Psychotherapy, and Psychosomatics, Humans, Prospective Studies, Antipsychotic Agents
Abstract

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 < 0.05). Lower doses were associated with increase in total and HDL cholesterol and systolic and diastolic blood pressure (p < 0.05), whereas higher doses were associated with glucose increases (p = 0.01). Patients receiving >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.

Published
2022

35. Metabolomic alteration induced by psychotropic drugs: Short‐term metabolite profile as a predictor of weight gain evolution

Author

Lenski, Marie, Sidibé, Jonathan, Gholam, Mehdi, Hennart, Benjamin, Dubath, Céline, Augsburger, Marc, von Gunten, Armin, Conus, Philippe, Allorge, Delphine, Thomas, Aurelien, Eap, Chin B., CHU Lille, Institut Pasteur de Lille, Université de Lille, IMPact de l'Environnement Chimique sur la Santé humaine (IMPECS) - ULR 4483, Hôpitaux Universitaires de Genève [HUG], Université de Lausanne = University of Lausanne [UNIL], Geneva University Hospital [HUG], Université de Lausanne = University of Lausanne (UNIL), Geneva University Hospital (HUG), Hôpitaux Universitaires de Genève (HUG), Impact de l'environnement chimique sur la santé humaine - ULR 4483 (IMPECS), and Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)

Subjects
Adult, Male, Psychotropic Drugs, Research, [SDV]Life Sciences [q-bio], Articles, RM1-950, Middle Aged, Weight Gain, Article, Cohort Studies, Humans, Metabolomics, Female, Therapeutics. Pharmacology, Public aspects of medicine, RA1-1270, Biomarkers, Kynurenine, Aged
Abstract

International audience; Psychotropic drugs can induce strong metabolic adverse effects, potentially increasing morbidity and/or mortality of patients. Metabolomic profiling, by studying the levels of numerous metabolic intermediates and products in the blood, allows a more detailed examination of metabolism dysfunctions. We aimed to identify blood metabolomic markers associated with weight gain in psychiatric patients. Sixty-two patients starting a treatment known to induce weight gain were recruited. Two hundred and six selected metabolites implicated in various pathways were analyzed in plasma, at baseline and after 1 month of treatment. Additionally, 15 metabolites of the kynurenine pathway were quantified. This latter analysis was repeated in a confirmatory cohort of 24 patients. Among the 206 metabolites, a plasma metabolomic fingerprint after 1 month of treatment embedded 19 compounds from different chemical classes (amino acids, acylcarnitines, carboxylic acids, catecholamines, nucleosides, pyridine, and tetrapyrrole) potentially involved in metabolic disruption and inflammation processes. The predictive potential of such early metabolite changes on 3 months of weight evolution was then explored using a linear mixed-effects model. Of these 19 metabolites, short-term modifications of kynurenine, hexanoylcarnitine, and biliverdin, as well as kynurenine/tryptophan ratio at 1 month, were associated with 3 months weight evolution. Alterations of the kynurenine pathway were confirmed by quantification, in both exploratory and confirmatory cohorts. Our metabolomic study suggests a specific metabolic dysregulation after 1 month of treatment with psychotropic drugs known to induce weight gain. The identified metabolomic signature could contribute in the future to the prediction of weight gain in patients treated with psychotropic drugs.

Published
2021

36. The psychosis metabolic risk calculator (PsyMetRiC) for young people with psychosis: International external validation and site-specific recalibration in two independent European samples

Author

Perry, Benjamin I., primary, Vandenberghe, Frederik, additional, Garrido-Torres, Nathalia, additional, Osimo, Emanuele F., additional, Piras, Marianna, additional, Vazquez-Bourgon, Javier, additional, Upthegrove, Rachel, additional, Grosu, Claire, additional, De La Foz, Victor Ortiz-Garcia, additional, Jones, Peter B., additional, Laaboub, Nermine, additional, Ruiz-Veguilla, Miguel, additional, Stochl, Jan, additional, Dubath, Celine, additional, Canal-Rivero, Manuel, additional, Mallikarjun, Pavan, additional, Delacrétaz, Aurélie, additional, Ansermot, Nicolas, additional, Fernandez-Egea, Emilio, additional, Crettol, Severine, additional, Gamma, Franziska, additional, Plessen, Kerstin J., additional, Conus, Philippe, additional, Khandaker, Golam M., additional, Murray, Graham K., additional, Eap, Chin B., additional, and Crespo-Facorro, Benedicto, additional

Published
2022
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39. N-acetylcysteine in a Double-Blind Randomized Placebo-Controlled Trial: Toward Biomarker-Guided Treatment in Early Psychosis

Author

Conus, Philippe, Seidman, Larry J, Fournier, Margot, Xin, Lijing, Cleusix, Martine, Baumann, Philipp S, Ferrari, Carina, Cousins, Ann, Alameda, Luis, Gholam-Rezaee, Mehdi, Golay, Philippe, Jenni, Raoul, Woo, T -U Wilson, Keshavan, Matcheri S, Eap, Chin B, Wojcik, Joanne, Cuenod, Michel, Buclin, Thierry, Gruetter, Rolf, and Do, Kim Q

Published
2018
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46. The psychosis metabolic risk calculator (PsyMetRiC) for young people with psychosis: International external validation and site-specific recalibration in two independent European samples

Author

National Institute for Health and Care Research (US), Cambridge Biomedical Research Centre, Wellcome Trust, Swiss National Science Foundation, Instituto de Salud Carlos III, Junta de Andalucía, Fundació Seny, Fundación Marques de Valdecilla, Ministerio de Economía y Competitividad (España), Perry, Benjamin I. [0000-0002-1533-026X], Vandenberghe, Frederik [0000-0002-8964-2047], Osimo, Emanuele F. [0000-0001-6239-5691], Perry, Benjamin I., Vandenberghe, Frederik, Garrido-Torres, Nathalia, Osimo, Emanuele F., Piras, Marianna, Vázquez-Bourgon, Javier, Upthegrove, Rachel, Grosu, Claire, Ortiz-Garcia de la Foz, Victor, Jones, Peter B., Laaboub, Nermine, Ruiz-Veguilla, Miguel, Stochl, Jan, Dubath, Celine, Canal-Rivero, Manuel, Mallikarjun, Pavan, Delacrétaz, Aurélie, Ansermot, Nicolas, Fernández-Egea, Emilio, Crettol, Severine, Gamma, Franziska, Plessen, Kerstin J., Conus, Philippe, Khandaker, Golam M., Murray, Graham K., Eap, Chin B., Crespo-Facorro, Benedicto, National Institute for Health and Care Research (US), Cambridge Biomedical Research Centre, Wellcome Trust, Swiss National Science Foundation, Instituto de Salud Carlos III, Junta de Andalucía, Fundació Seny, Fundación Marques de Valdecilla, Ministerio de Economía y Competitividad (España), Perry, Benjamin I. [0000-0002-1533-026X], Vandenberghe, Frederik [0000-0002-8964-2047], Osimo, Emanuele F. [0000-0001-6239-5691], Perry, Benjamin I., Vandenberghe, Frederik, Garrido-Torres, Nathalia, Osimo, Emanuele F., Piras, Marianna, Vázquez-Bourgon, Javier, Upthegrove, Rachel, Grosu, Claire, Ortiz-Garcia de la Foz, Victor, Jones, Peter B., Laaboub, Nermine, Ruiz-Veguilla, Miguel, Stochl, Jan, Dubath, Celine, Canal-Rivero, Manuel, Mallikarjun, Pavan, Delacrétaz, Aurélie, Ansermot, Nicolas, Fernández-Egea, Emilio, Crettol, Severine, Gamma, Franziska, Plessen, Kerstin J., Conus, Philippe, Khandaker, Golam M., Murray, Graham K., Eap, Chin B., and Crespo-Facorro, Benedicto

Abstract

[Background]: Cardiometabolic dysfunction is common in young people with psychosis. Recently, the Psychosis Metabolic Risk Calculator (PsyMetRiC) was developed and externally validated in the UK, predicting up-to six-year risk of metabolic syndrome (MetS) from routinely collected data. The full-model includes age, sex, ethnicity, body-mass index, smoking status, prescription of metabolically-active antipsychotic medication, high-density lipoprotein, and triglyceride concentrations; the partial-model excludes biochemical predictors., [Methods]: To move toward a future internationally-useful tool, we externally validated PsyMetRiC in two independent European samples. We used data from the PsyMetab (Lausanne, Switzerland) and PAFIP (Cantabria, Spain) cohorts, including participants aged 16–35y without MetS at baseline who had 1–6y follow-up. Predictive performance was assessed primarily via discrimination (C-statistic), calibration (calibration plots), and decision curve analysis. Site-specific recalibration was considered., [Findings]: We included 1024 participants (PsyMetab n=558, male=62%, outcome prevalence=19%, mean follow-up=2.48y; PAFIP n=466, male=65%, outcome prevalence=14%, mean follow-up=2.59y). Discrimination was better in the full- compared with partial-model (PsyMetab=full-model C=0.73, 95% C.I., 0.68–0.79, partial-model C=0.68, 95% C.I., 0.62–0.74; PAFIP=full-model C=0.72, 95% C.I., 0.66–0.78; partial-model C=0.66, 95% C.I., 0.60–0.71). As expected, calibration plots revealed varying degrees of miscalibration, which recovered following site-specific recalibration. PsyMetRiC showed net benefit in both new cohorts, more so after recalibration., [Interpretation]: The study provides evidence of PsyMetRiC's generalizability in Western Europe, although further local and international validation studies are required. In future, PsyMetRiC could help clinicians internationally to identify young people with psychosis who are at higher cardiometabolic risk, so interventions can be directed effectively to reduce long-term morbidity and mortality.

Published
2022

47. An International Adult Guideline for Making Clozapine Titration Safer by Using Six Ancestry-Based Personalized Dosing Titrations, CRP, and Clozapine Levels

Author

de Leon, Jose, Schoretsanitis, Georgios, Smith, Robert L., Molden, Espen, Solismaa, Anssi, Seppala, Niko, Kopecek, Miloslav, Svancer, Patrik, Olmos, Ismael, Ricciardi, Carina, Iglesias-Garcia, Celso, Iglesias-Alonso, Ana, Spina, Edoardo, Ruan, Can-Jun, Wang, Chuan-Yue, Wang, Gang, Tang, Yi-Lang, Lin, Shih-Ku, Lane, Hsien-Yuan, Kim, Yong Sik, Kim, Se Hyun, Rajkumar, Anto P., Gonzalez-Esquivel, Dinora F., Jung-Cook, Helgi, Baptista, Trino, Rohde, Christopher, Nielsen, Jimmi, Verdoux, Helene, Quiles, Clelia, Sanz, Emilio J., De las Cuevas, Carlos, Cohen, Dan, Schulte, Peter F. J., Ertugrul, Aygun, Chopra, Nitin, McCollum, Betsy, Shelton, Charles, Cotes, Robert O., Kaithi, Arun R., Kane, John M., Farooq, Saeed, Ng, Chee H., Bilbily, John, Hiemke, Christoph, Lopez-Jaramillo, Carlos, McGrane, Ian, Lana, Fernando, Eap, Chin B., Arrojo-Romero, Manuel, Seifritz, Erich, Every-Palmer, Susanna, Bousman, Chad A., Bebawi, Emmanuel, Bhattacharya, Rahul, Kelly, Deanna L., Otsuka, Yuji, Lazary, Judit, Torres, Rafael, Yecora, Agustin, Motuca, Mariano, Chan, Sherry K. W., Zolezzi, Monica, Ouanes, Sami, De Berardis, Domenico, Grover, Sandeep, Procyshyn, Ric M., Adebayo, Richard A., Kirilochev, Oleg O., Soloviev, Andrey, Fountoulakis, Konstantinos N., Wilkowska, Alina, Ayub, Muhammad, Silva, Alzira, Bonelli, Raphael M., Villagran-Moreno, Jose M., Crespo-Facorro, Benedicto, Temmingh, Henk, Decloedt, Eric, Pedro, Maria R., Takeuchi, Hiroyoshi, Tsukahara, Masaru, Gruender, Gerhard, Sagud, Marina, Celofiga, Andreja, Ristic, Dragana Ignjatovic, Ortiz, Bruno B., Elkis, Helio, Palha, Antonio J. Pacheco, LLerena, Adrian, Fernandez-Egea, Emilio, Siskind, Dan, Weizman, Abraham, Masmoudi, Rim, Saffian, Shamin Mohd, Leung, Jonathan G., Buckley, Peter F., Marder, Stephen R., Citrome, Leslie, Freudenreich, Oliver, Correll, Christoph U., Muller, Daniel J., Anil Yagcioglu, A. Elif, Radulescu, Flavian S., Cubala, Wieslaw J., de Leon, Jose, Schoretsanitis, Georgios, Smith, Robert L., Molden, Espen, Solismaa, Anssi, Seppala, Niko, Kopecek, Miloslav, Svancer, Patrik, Olmos, Ismael, Ricciardi, Carina, Iglesias-Garcia, Celso, Iglesias-Alonso, Ana, Spina, Edoardo, Ruan, Can-Jun, Wang, Chuan-Yue, Wang, Gang, Tang, Yi-Lang, Lin, Shih-Ku, Lane, Hsien-Yuan, Kim, Yong Sik, Kim, Se Hyun, Rajkumar, Anto P., Gonzalez-Esquivel, Dinora F., Jung-Cook, Helgi, Baptista, Trino, Rohde, Christopher, Nielsen, Jimmi, Verdoux, Helene, Quiles, Clelia, Sanz, Emilio J., De las Cuevas, Carlos, Cohen, Dan, Schulte, Peter F. J., Ertugrul, Aygun, Chopra, Nitin, McCollum, Betsy, Shelton, Charles, Cotes, Robert O., Kaithi, Arun R., Kane, John M., Farooq, Saeed, Ng, Chee H., Bilbily, John, Hiemke, Christoph, Lopez-Jaramillo, Carlos, McGrane, Ian, Lana, Fernando, Eap, Chin B., Arrojo-Romero, Manuel, Seifritz, Erich, Every-Palmer, Susanna, Bousman, Chad A., Bebawi, Emmanuel, Bhattacharya, Rahul, Kelly, Deanna L., Otsuka, Yuji, Lazary, Judit, Torres, Rafael, Yecora, Agustin, Motuca, Mariano, Chan, Sherry K. W., Zolezzi, Monica, Ouanes, Sami, De Berardis, Domenico, Grover, Sandeep, Procyshyn, Ric M., Adebayo, Richard A., Kirilochev, Oleg O., Soloviev, Andrey, Fountoulakis, Konstantinos N., Wilkowska, Alina, Ayub, Muhammad, Silva, Alzira, Bonelli, Raphael M., Villagran-Moreno, Jose M., Crespo-Facorro, Benedicto, Temmingh, Henk, Decloedt, Eric, Pedro, Maria R., Takeuchi, Hiroyoshi, Tsukahara, Masaru, Gruender, Gerhard, Sagud, Marina, Celofiga, Andreja, Ristic, Dragana Ignjatovic, Ortiz, Bruno B., Elkis, Helio, Palha, Antonio J. Pacheco, LLerena, Adrian, Fernandez-Egea, Emilio, Siskind, Dan, Weizman, Abraham, Masmoudi, Rim, Saffian, Shamin Mohd, Leung, Jonathan G., Buckley, Peter F., Marder, Stephen R., Citrome, Leslie, Freudenreich, Oliver, Correll, Christoph U., Muller, Daniel J., Anil Yagcioglu, A. Elif, Radulescu, Flavian S., and Cubala, Wieslaw J.

Abstract

This international guideline proposes improving clozapine package inserts worldwide by using ancestry-based dosing and titration. Adverse drug reaction (ADR) databases suggest that clozapine is the third most toxic drug in the United States (US), and it produces four times higher worldwide pneumonia mortality than that by agranulocytosis or myocarditis. For trough steady-state clozapine serum concentrations, the therapeutic reference range is narrow, from 350 to 600 ng/mL with the potential for toxicity and ADRs as concentrations increase. Clozapine is mainly metabolized by CYP1A2 (female non-smokers, the lowest dose; male smokers, the highest dose). Poor metabolizer status through phenotypic conversion is associated with co-prescription of inhibitors (including oral contraceptives and valproate), obesity, or inflammation with C-reactive protein (CRP) elevations. The Asian population (Pakistan to Japan) or the Americas' original inhabitants have lower CYP1A2 activity and require lower clozapine doses to reach concentrations of 350 ng/mL. In the US, daily doses of 300-600 mg/day are recommended. Slow personalized titration may prevent early ADRs (including syncope, myocarditis, and pneumonia). This guideline defines six personalized titration schedules for inpatients: 1) ancestry from Asia or the original people from the Americas with lower metabolism (obesity or valproate) needing minimum therapeutic dosages of 75-150 mg/day, 2) ancestry from Asia or the original people from the Americas with average metabolism needing 175-300 mg/day, 3) European/Western Asian ancestry with lower metabolism (obesity or valproate) needing 100-200 mg/day, 4) European/Western Asian ancestry with average metabolism needing 250-400 mg/day, 5) in the US with ancestries other than from Asia or the original people from the Americas with lower clozapine metabolism (obesity or valproate) needing 150-300 mg/day, and 6) in the US with ancestries other than from Asia or the original people fr

Published
2022

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

Author

Schoretsanitis, Georgios; https://orcid.org/0000-0002-3851-4117, Dubath, Céline, Grosu, Claire, Piras, Marianna, Laaboub, Nermine, Ranjbar, Setareh, Ansermot, Nicolas, Crettol, Séverine; https://orcid.org/0000-0003-3790-7194, Vandenberghe, Frederik, Gamma, Franziska, von Gunten, Armin, Plessen, Kerstin Jessica, Seifritz, Erich; https://orcid.org/0000-0002-7311-4426, Conus, Philippe, Eap, Chin B; https://orcid.org/0000-0002-5439-0230, Schoretsanitis, Georgios; https://orcid.org/0000-0002-3851-4117, Dubath, Céline, Grosu, Claire, Piras, Marianna, Laaboub, Nermine, Ranjbar, Setareh, Ansermot, Nicolas, Crettol, Séverine; https://orcid.org/0000-0003-3790-7194, Vandenberghe, Frederik, Gamma, Franziska, von Gunten, Armin, Plessen, Kerstin Jessica, Seifritz, Erich; https://orcid.org/0000-0002-7311-4426, Conus, Philippe, and Eap, Chin B; https://orcid.org/0000-0002-5439-0230

Abstract

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 < 0.05). Lower doses were associated with increase in total and HDL cholesterol and systolic and diastolic blood pressure (p < 0.05), whereas higher doses were associated with glucose increases (p = 0.01). Patients receiving >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.

Published
2022

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