A systematic review of pharmacogenetic testing to guide antipsychotic treatment.

Pharmacogenomics could optimize antipsychotic treatment by preventing adverse drug reactions, improving treatment efficacy or relieving the cost burden on the healthcare system. Here we conducted a systematic review to investigate whether pharmacogenetic testing in individuals undergoing antipsychotic treatment influences clinical or economic outcomes. On 12 January 2024, we searched MEDLINE, EMBASE, PsycINFO and Cochrane Centrale Register of Controlled Trials. The results were summarized using a narrative approach and summary tables. In total, 13 studies were eligible for inclusion in the systematic review. The current evidence base is either in favor of pharmacogenetics-guided prescribing or showed no difference between pharmacogenetics and treatment as usual for clinical and economic outcomes. In the future, we require randomized controlled trials with sufficient sample sizes that provide recommendations for patients who take antipsychotics based on a broad, multigene panel, with consistent and comparable clinical outcomes.

Impact of high prebiotic and probiotic dietary education in the SARS-CoV-2 era: improved cardio-metabolic profile in schizophrenia spectrum disorders.

BACKGROUND: The development of new aetiological premises, such as the microbiota-gut-brain axis theory, evidences the influence of dietary and nutritional patterns on mental health, affecting the patient's quality of life in terms of physical and cardiovascular health. The aim was to determine the impact of a nutritional programme focused on increasing the intake of prebiotic and probiotic food on cardio-metabolic status in individuals with schizophrenia spectrum disorders in the contextual setting of the SARS-CoV-2 era. METHODS: A randomised clinical trial (two-arm, double-blind, balanced-block, six-month intervention) was conducted in a group of 50 individuals diagnosed with schizophrenia spectrum disorder during the SARS-CoV-2 confinement period. The control group received conventional dietary counselling on an individual basis. In the intervention group, an individual nutritional education programme with a high content of prebiotics and probiotics (dairy and fermented foods, green leafy vegetables, high-fibre fruit, whole grains, etc.) was established. Data on cardiovascular status were collected at baseline, three and six months. In addition, anthropometric parameters were analysed monthly. RESULTS: Forty-four subjects completed follow-up and were analysed. Statistical differences (p < 0.05) were found in all anthropometric variables at baseline and six months of intervention. A 27.4% reduction in the prevalence of metabolic syndrome risk factors in all its components was evidenced, leading to a clinically significant improvement (decrease in cardiovascular risk) in the intervention group at six months. CONCLUSIONS: The development of a nutritional programme focused on increasing the dietary content of prebiotics and probiotics effectively improves the cardio-metabolic profile in schizophrenia spectrum disorders. Therefore, nursing assumes an essential role in the effectiveness of dietary interventions through nutritional education and the promotion of healthy lifestyles. Likewise, nursing acquires a relevant role in interdisciplinary coordination in confinement contexts. TRIAL REGISTRATION: The study protocol complied with the Declaration of Helsinki for medical studies; the study received ethical approval from referral Research Ethics Committee in November 2019 (reg. no. 468) and retrospectively registered in clinicaltrials.gov (NCT04366401. First Submitted: 28th April 2020; First Registration: 25th June 2020).

Síndrome metabólico iatrogénico derivado del uso de antipsicóticos de segunda generación / Iatrogenic metabolic syndrome derived of the use of second-generation antipsychotics

Objetivo: aportar evidencias sobre los factores determinantes del síndrome metabólico iatrogénico derivado del uso de antipsicóticos de segunda generación. Métodos: se llevó a cabo una revisión narrativa entre enero y febrero de 2020. Para ello se realizaron búsquedas bibliográficas en distintas bases de datos y plataformas: Pubmed, ScienceDirect, Google Scholar y UpToDate. Se usaron las siguientes palabras clave (MeSH/DeCS): antipsicóticos (antipsychotic agents), antipsicóticos atípicos (atypical antipsychotics), síndromemetabólico (metabolic syndrome), Enfermería (nursing), efectos adversos (side effects), salud mental (mental Health). Criterios de inclusión: idioma español e inglés, publicaciones originales y a texto completo de los últimos cinco años, estudio en humanos.Resultados: se seleccionaron 32 artículos. La evidencia establece la clozapina, olanzapina y paliperidona como principales antipsicóticos de segunda generación que favorecen el síndrome metabólico. Sería conveniente realizar controles antropométricos y bioquímicos: tensión arterial, peso, perímetro abdominal, índice de masa corporal (IMC), glucosa, HDL y triglicéridos. Se necesita un abordaje terapéutico multimodal para prevenir el síndrome metabólico, mejorar la educación sanitaria en estilos de vida saludable y considerar la polifarmacia homeostática. Enfermería asume un rol destacado, mediante la utilización de herramientas de valoración centradas en farmacovigilancia, sexualidad y calidad de vida. Conclusiones: se precisa el diseño de políticas sanitarias de calidad acordes con las expectativas y necesidades de la población psiquiátrica, promoviendo estilos de vida saludable y atención psicofarmacológica ante el elevado riesgo cardiovascular.La Enfermería de Salud Mental se conforma como piedra angular en la atención, prevención, coordinación y el seguimiento comunitario del síndrome metabólico iatrogénico.(AU)

Objective: to provide evidence about the factors determining iatrogenic metabolic syndrome derived of the use of second-generation antipsychotics. Methods: a narrative review was conducted between January and February 2020. This entailed bibliographic searches in different databases and platforms: Pubmed, Science Direct, Google Scholar and UpToDate. The following key words were used (MeSH/DeCS): antipsychotic agents (antipsicóticos), atypical antipsychotics (antipsicóticos atípicos), metabolic syndrome (síndrome metabólico), Nursing (enfermería), side effects (efectos adversos), mental health (salud mental). Inclusion criteria: Spanish and English languages, original and full-text publications from the last five years, studies in human beings. Results: in total, 32 articles were retrieved. Evidence determined that clozapine, olanzapine and paliperidone were the main second-generation antipsychotics contributing to metabolic syndrome. It would be convenient to conduct anthropometric and biochemical monitoring: blood pressure, weight, abdominal perimeter, body mass index (BMI), glucose, HDL and triglycerides. A multimodal treatment approach is needed to prevent metabolic syndrome, as well as an improvement in healthcare education regarding healthy lifestyles, and considering homeostatic polypharmacy. Nursing plays a leading role by using assessment tools focused on pharmacovigilance, sexuality and quality of life. Conclusions: healthcare policies must be designed according to the expectations and needs of the psychiatric population, promoting healthy lifestyles and psychopharmacological care due to the high cardiovascular risk. Mental Health Nursing becomes a cornerstone for the care, prevention, coordination and community follow-up of iatrogenic metabolic syndrome.(AU)

Review: Influence of the CYP450 Genetic Variation on the Treatment of Psychotic Disorders.

Second-generation antipsychotic metabolism is mainly carried out by the CYP450 superfamily, which is highly polymorphic. Therefore, knowing the influence of the different known CYP450 polymorphisms on antipsychotic plasmatic levels and, consequently, the biological effect could contribute to a deeper knowledge of interindividual antipsychotic treatment variability, prompting possible solutions. Considering this, this state of the art review aimed to summarize the current knowledge about the influence of the diverse characterized phenotypes on the metabolism of the most used second-generation antipsychotics. Forty studies describing different single nucleotide polymorphisms (SNPs) associated with the genes CYP1A2, CYP2D6, CYP3A4, CYP3A5, and ABCB1 and their influence on pharmacokinetics of olanzapine, clozapine, aripiprazole, risperidone, and quetiapine. Most of the authors concluded that although significant differences in the pharmacokinetic parameters between the different phenotypes could be observed, more thorough studies describing pharmacokinetic interactions and environmental conditions, among other variables, are needed to fully comprehend these pharmacogenetic interactions.

Economic Impact of the Application of a Precision Medicine Model (5SPM) on Psychotic Patients.

BACKGROUND: Schizophrenia is a severe mental disorder that often manifests within the first three decades of life. Its prognosis is uncertain and may result in a prolonged treatment that could extend throughout the entire lifespan of the patient. Antipsychotic drugs are characterized by a high interindividual variability when considering therapeutic effect and emergence of adverse effects. Such interindividual variability is thought to be associated primarily with pharmacokinetic matters. OBJECTIVE: The objective of this study was to evaluate the economic impact of the application of the 5-Step Precision Medicine model (5SPM), an approach based on the pharmacogenetic analysis of the primary genes involved in the metabolism of the therapy for each patient, restructuring treatment as necessary. PATIENTS AND METHODS: One hundred eighty-eight psychiatry patients were analysed for single nucleotide polymorphisms on genes CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP3A5 and ABCB1. Information on patients' diagnosis, pharmacotherapy, and hospitalizations was collected. RESULTS: We achieved a cost-benefit ratio of 3.31-3.59 with a reduction of direct cost (hospitalizations plus pharmacotherapy) with a reduction of total cost in 67% of the patients who underwent the clinical intervention. CONCLUSION: A rational Precision Medicine-based approach to psychiatric patients could result in a reduction on number of drugs required to control exacerbations, and the underlying pathologies, reducing the risk of adverse effects and improving adherence to treatment, leading to a potential decrease in direct costs. This methodology has been shown to be cost-dominant and, being based on a pharmacogenetic analysis, it has a lifelong nature, as the data obtained can be applied to other medical disciplines.

Case Report: Pharmacogenetics Applied to Precision Psychiatry Could Explain the Outcome of a Patient With a New CYP2D6 Genotype.

Precision medicine applied to psychiatry provides new insight into the promising field of precision psychiatry. Psychotic disorders are heterogeneous, complex, chronic, and severe mental disorders. Not only does the prognosis and the course of the disease vary among patients suffering from psychotic disorders, but the treatment response varies as well. Although antipsychotic drugs are the cornerstone of the treatment of schizophrenia, many patients only partially respond to these drugs. Furthermore, patients often experience adverse events which can lead to poor treatment adherence. Interindividual variability in drug response could be related to age, gender, ethnicity, lifestyle factors, pharmacological interactions, obesity, and genetics, all of which influence the process of drug metabolism. Commonly prescribed antipsychotics are metabolized by cytochrome P450 (CYP450) enzymes, and CYP450 genes are highly polymorphic. Pharmacogenetic testing is increasingly being used to predict a patient's drug response and could help to find the most appropriate therapy for an individual patient. In this report, we describe a psychotic patient who did not receive adequate clinical follow-up and subsequently presented adverse events, which could be explained by his pharmacogenetic profile and the drug interactions resulting from the polypharmacy prescribed.

Application of a Pharmacogenetics-Based Precision Medicine Model (5SPM) to Psychotic Patients That Presented Poor Response to Neuroleptic Therapy.

Antipsychotics are the keystone of the treatment of severe and prolonged mental disorders. However, there are many risks associated with these drugs and not all patients undergo full therapeutic profit from them. The application of the 5 Step Precision Medicine model(5SPM), based on the analysis of the pharmacogenetic profile of each patient, could be a helpful tool to solve many of the problematics traditionally associated with the neuroleptic treatment. In order to solve this question, a cohort of psychotic patients that showed poor clinical evolution was analyzed. After evaluating the relationship between the prescribed treatment and pharmacogenetic profile of each patient, a great number of pharmacological interactions and pharmacogenetical conflicts were found. After reconsidering the treatment of the conflictive cases, patients showed a substantial reduction on mean daily doses and polytherapy cases, which may cause less risk of adverse effects, greater adherence, and a reduction on economic costs.