The usefulness of Olanzapine plasma concentrations in monitoring treatment efficacy and metabolic disturbances in first-episode psychosis

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Abstract

Introduction

The role of Olanzapine therapeutic drug monitoring is controversial. The present study explores the associations of Olanzapine plasma concentrations with clinical response and metabolic side effects in first episode psychosis (FEP) after 2 months of treatment.

Methods

Forty-seven patients were included. Improvement in clinical symptomatology was assessed using the PANSS. Metabolic assessment included weight, blood pressure, waist circumference, blood glucose, total cholesterol, high-density lipoprotein, low-density lipoprotein, and triglycerides.

Results

The Olanzapine plasma concentrations after 2 months of treatment were positively correlated with weight gain (r = 0.49, p = 0.003), and a concentration > 23.28 ng/mL was identified as a positive predictor of weight gain (≥ 7%). The Olanzapine concentration to dose (C/D) ratio was positively correlated with the percentage of improvement in the total PANSS (r = 0.46, p = 0.004), and a C/D ratio > 2.12 was identified as a positive predictor of a good response (percentage of improvement > 30%) after 2 months of treatment. We also identified several factors that could alter Olanzapine pharmacokinetics: gender (p = 0.03), diagnosis (p = 0.05), smoking habit (p = 0.05), and co-medications such as valproic acid (p = 0.05) and anxiolytics (p = 0.01).

Discussion

In conclusion, our results suggest that therapeutic drug monitoring of Olanzapine could be helpful to evaluate therapeutic efficacy and metabolic dysfunction in FEP patients treated with Olanzapine.

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Acknowledgements

This study was supported by the Ministerio de Economía y Competitividad (Ref. ISCIII: PI 080208, PI0/00,283 and PI14/00,612)—Instituto de Salud Carlos III—Fondo Europeo de Desarrollo Regional (FEDER)-Unión Europea; the Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM); and by the CERCA Programme / the Government of Catalonia, Secretaria d’Universitats i Recerca del Departament d’Economia i Coneixement (2017SGR1562; 2017SGR1355; 2017SGR881). Dr. Vieta thanks the support of the Spanish Ministry of Science, Innovation and Universities (PI15/00283) integrated into the Plan Nacional de I+D+I y cofinanciado por el ISCIII-Subdirección General de Evaluación y el Fondo Europeo de Desarrollo Regional (FEDER); CIBERSAM; and the Comissionat per a Universitats i Recerca del DIUE de la Generalitat de Catalunya to the Bipolar Disorders Group (2017 SGR 1365) and the project SLT006/17/00357, from PERIS 2016-2020 (Departament de Salut). CERCA Programme/Generalitat de Catalunya.

PEPs Group: Torra, Mercè (Pharmacology and Toxicology Department, CDB, Hospital Clínic de Barcelona, Barcelona, Spain); Llerena, Adrian (CICAB Clinical Research Center, Extremadura University Hospital and Medical School, Servicio Extremeño de Salud, Badajoz, Spain. CIBERSAM, Spain); Anmella, Gerard and Colomer, Lluc (Hospital Clinic of Barceo Neuroscience Institute, ; IDIBAPS; CIBERSAM, Barcelona, Spain); Moreno, Carmen and Durán-Cutilla, Manuel (Department of Child and Adolescent Psychiatry, Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), School of Medicine, Universidad Complutense, Madrid, Spain; CIBERSAM, Madrid, Spain); Alonso Solís, Anna and Grasa, Eva (Biomedical Research Institute Sant Pau (IIB-SANT PAU), Hospital de la Santa Creu i Sant Pau; Universitat Autònoma de Barcelona (UAB), Barcelona, Spain. Mental Health Networking Biomedical Research Centre, CIBERSAM); Lopez, Puri and García, Sainza (Department of Psychiatry, Hospital Universitario de Alava, Vitoria, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain); De-la-Cámara, Concepción (Hospital Clínico Universitario and Instituto de Investigación Sanitaria (IIS) Aragón, Zaragoza. Department of Medicine and Psychiatry; Universidad de Zaragoza; CIBERSAM, Spain); Saz, Pedro (Department of Medicine and Psychiatry, Zaragoza University; Instituto de Investigación Sanitaria Aragón (IIS Aragón), Zaragoza); Moltó, Maria Dolores Department of Genetics, University of Valencia, Campus of Burjassot, Valencia, Spain. CIBERSAM; Biomedical Research Institute INCLIVA, Valencia, Spain; Hernandez Viadel, Miguel (Department of Psychiatry, Cinical Hospital of Valencia, Valencia, Spain. CIBERSAM, Spain; Biomedical Research Institute INCLIVA, Valencia, Spain) ; Casanovas, Francesc and SanAgustin, David (Hospital del Mar Medical Research Institute (IMIM)); Castro-Fornieles, Josefina and de la Serna, Elena (Department of Child and Adolescent Psychiatry and Psychology, Clínic Institute of Neurosciences, Hospital Clínic de Barcelona, 2017SGR881, University of Barcelona, CIBERSAM, IDIBAPS, Barcelona, Spain); Contreras, Fernando and Saiz, Cristina (Psychiatric Service, Bellvitge Universitary Hospital, IDIBELL, University of Barcelona, CIBERSAM); Bobes, Julio and García-Portilla, María Paz (Área de Psiquiatría, Universidad de Oviedo, Hospital Universitario Central de Asturias (HUCA); Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain; Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Spain); Gutierrez Fraile, Miguel (Araba University Hospital, Bioaraba Research Institute, Psychiatry, Vitoria, Spain; University of the Basque Country (UPV/EHU), Department of Neurosciences; CIBERSAM); Zabala Rabadán, Arantzazu (UPV/EHU, Department of Neurosciences; CIBERSAM; BioCruces Health Research Institute, Vizcaya, Spain.); Rodríguez-Jimenez, Roberto (Instituto de Investigación Sanitaria Hospital 12 de Octubre (imas12), Madrid, Spain; CIBERSAM; CogPsy Group, Universidad Complutense de Madrid (UCM), Madrid, Spain); Fares-Otero, Natalia E. (Instituto de Investigación Sanitaria Hospital 12 de Octubre (imas12), Madrid, Spain); Usall, Judith (Instituto de Investigación Sanitaria Hospital 12 de Octubre (imas12), Madrid, Spain); Butjosa, Anna (Research and Development Unit, Parc Sanitari Sant Joan de Déu, Sant Boi de Llobregat, Barcelona; Hospital Materno- Infantil Sant Joan de Déu, Esplugues de Llobregat, Barcelona, Catalonia); Sarró, Salvador and Pomarol-Clotet, Edith (FIDMAG Germanes Hospitalàries Research Foundation , Barcelona, Spain. Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM); Ibañez. Angela (Department of Psychiatry, Hospital Universitario Ramón y Cajal, IRYCIS, Universidad de Alcalá, Madrid, Spain; Biomedical Research Networking Center for Mental Health (CIBERSAM). Madrid ,Spain); Ribeiro, Marta (Department of Psychiatry, Complejo Hospitalario de Navarra, Pamplona, Spain. IdiSNA, Navarra Institute for Health Research, Pamplona, Spain); Balanzá-Martínez, Vicent (Teaching Unit of Psychiatry and Psychological Medicine. Department of Medicine, Universitat de València. CIBERSAM. Hospital Clínico Universitario de Valencia. INCLIVA).

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Contributions

The results presented here are part of a broader project, the PEPs study. Bernardo M is the coordinator of the PEPs study. Saiz J is the coordinator of the pharmacogenetic’s module. Cuesta MJ, Fraguas D, Lobo A, González-Pinto A, Díaz-Canjea MC, Corripio I, Vieta E, Baeza I, Mané A, and García-Rizo C are the coordinators of their research centers and participated in the recruitment and assessment of the sample. Bioque M, Mezquida G, and Amoretti S participated in the coordination of the sample shipment, the maintenance of the PEPs database and in the recruitment, and assessment of the sample. Arnaiz JA and Rodrigues-Silva C designed and performed the statistical analysis under the supervision of Mas S and wrote the first draft of the manuscript. Authors listed in the PEPs group acronym participated in the recruitment and assessment of the sample. Llerena A was responsible of the TaqMan® analyses and Torra M performed the drug plasma determinations All the authors, including the PEPs group authors listed in the acronym, contributed to the final draft of the manuscript.

Corresponding author

Correspondence to S. Mas.

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Conflict of interest

C. De-la-Camara received financial support to attend scientific meetings from Janssen-Cilag, Almirall, Eli Lilly, Lundbeck, Rovi, Esteve, Novartis, and Astrazeneca. E. Vieta has received grants and served as consultant, advisor or CME speaker for the following entities: Abbott, Allergan, Angelini, Dainippon Sumitomo Pharma, Janssen, Lundbeck, Novartis, Otsuka, Richter, Sage, Sanofi-Aventis, and Takeda. M. Bernardo has been a consultant for, received grant/research support and honoraria from, and been on the speakers/advisory board of ABBiotics, Adamed, Angelini, Casen Recordati, Eli Lilly, Janssen-Cilag, Lundbeck, Otsuka, Takeda, and Somatics and has obtained research funding from the Ministry of Education, Culture and Sport, the Spanish Ministry of Economy, Industry and Competitiveness (CIBERSAM), by the Government of Catalonia, Secretaria d’Universitats i Recerca del Departament d’Economia i Coneixement (2017SGR1355), Foundation European Group for Research In Schizophrenia (EGRIS), and the 7th Framework Program of the European Union.

M. Bioque has received honoraria from talks and consultancy of Adamed, has received honoraria from consultancy of Ferrer, has received research support and honoraria from talks and consultancy of Janssen-Cilag, has received honoraria from talks and consultancy of Lundbeck, has received honoraria from talks and consultancy of Otsuka, and a research prize from Pfizer. R. Rodriguez-Jimenez has been a consultant for, spoken in activities of, or received grants from: Instituto de Salud Carlos III, Fondo de Investigación Sanitaria (FIS), Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid Regional Government (S2010/ BMD-2422 AGES), JanssenCilag, Lundbeck, Otsuka, Pfizer, Ferrer, Juste, Takeda, Exeltis, Angelini, and Casen-Recordati. V Balanzá-Martínez has been a consultant, advisor or Continuing Medical Education (CME) speaker over the last 3 years for the following entities: Angelini; Ferrer; Lundbeck; Nutrición Médica; and Otsuka. All other authors declare that they have no conflict of interest.

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Arnaiz, J.A., Rodrigues-Silva, C., Mezquida, G. et al. The usefulness of Olanzapine plasma concentrations in monitoring treatment efficacy and metabolic disturbances in first-episode psychosis. Psychopharmacology 238, 665–676 (2021). https://doi.org/10.1007/s00213-020-05715-5

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Keywords

  • Olanzapine
  • Therapeutic drug monitoring
  • Pharmacokinetics
  • First-episode psychosis
  • Drug level
  • Efficacy
  • Weight gain