Pharmacogenetic study of antipsychotic induced acute extrapyramidal symptoms in a first episode psychosis cohort: role of dopamine, serotonin and glutamate candidate genes

Mas, Sergi; Gassó, Patricia; Lafuente, Amàlia; Bioque, Miquel; Lobò, Antonio; González‐Pinto, Ana; Olmeda, M S; Corripio, Iluminada; LLerena, Adrián; Cabrera, Bibiana; Sáiz-Ruiz, Jerónimo; Bernardo, Miquel; Mezquida, Gisela; Meseguer, Ana; Bernardo, Enrique García; Parellada, Mara; Alonso-Solís, Anna; Grasa, Eva; Hernandez, Miryam Fernández; Cengotitabengoa, M. Martínez; Barcones, Fe; Arbej, Julio; Sanjuán, Julio; Aguilar, Eduardo J.; Balbuena, Antonio; Mané, Anna; Torrent, Carla; Vieta, Eduard; Baeza, Immaculada; Serna, Elena de la; Contreras, Fernando Hernández; Albacete, Auria; García-Portilla, María Paz; Bobes, Julio; Rabadán, Arantzazu Zabala; Echevarría, Rafael Segarra; Morales‐Muñoz, Isabel; Rodríguez‐Jiménez, Roberto; Butjosa, Anna; Rodié, Judith Usall i; Sarró, Salvador; Landín-Romero, Ramón; Cuadrado, Ángela Ibáñez; Cuesta, Manuel J.; Balanzá‐Martínez, Vicent

doi:10.1038/tpj.2016.44

Cited by 32 publications

(17 citation statements)

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“…Hundred and thirteen patients (43 cases with EPS and 70 controls without) from the PEPs study ( Phenotype–genotype and environmental interaction: application of a predictive model in first psychotic episodes ) treated with the same APs as in Replication Sample 1 (amisulpride, paliperidone, risperidone, and ziprasidone) 16 . The complete clinical protocol used in the PEPs project was previously published elsewhere 17 .…”

Section: Methodsmentioning

confidence: 99%

Improving pharmacogenetic prediction of extrapyramidal symptoms induced by antipsychotics

et al. 2018

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In previous work we developed a pharmacogenetic predictor of antipsychotic (AP) induced extrapyramidal symptoms (EPS) based on four genes involved in mTOR regulation. The main objective is to improve this predictor by increasing its biological plausibility and replication. We re-sequence the four genes using next-generation sequencing. We predict functionality “in silico” of all identified SNPs and test it using gene reporter assays. Using functional SNPs, we develop a new predictor utilizing machine learning algorithms (Discovery Cohort, N = 131) and replicate it in two independent cohorts (Replication Cohort 1, N = 113; Replication Cohort 2, N = 113). After prioritization, four SNPs were used to develop the pharmacogenetic predictor of AP-induced EPS. The model constructed using the Naive Bayes algorithm achieved a 66% of accuracy in the Discovery Cohort, and similar performances in the replication cohorts. The result is an improved pharmacogenetic predictor of AP-induced EPS, which is more robust and generalizable than the original.

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Section: Methodsmentioning

confidence: 99%

Improving pharmacogenetic prediction of extrapyramidal symptoms induced by antipsychotics

et al. 2018

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“…(2016) reported higher frequency (41%) of risperidone-induced EPS in Spanish patients with a first psychotic episode. [41] Further, based on a systematic review, risperidone was associated with more incidences of EPS than clozapine, olanzapine, quetiapine, and ziprasidone.…”

Section: Discussionmentioning

confidence: 99%

Risperidone-Induced Adverse Drug Reactions and Role of DRD2 (−141 C Ins/Del) and 5HTR2C (−759 C>T) Genetic Polymorphisms in Patients with Schizophrenia

Alladi

Mohan

Shewade

et al. 2017

Journal of Pharmacology and Pharmacotherapeutics

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Objective:To determine the adverse drug reaction (ADR) profile of risperidone and their association with dopamine (DRD2 − 141 C Ins/Del/rs1799732) and serotonin receptor (5HTR2C −759 C>T/rs3813929) gene polymorphisms in patients with schizophrenia.Materials and Methods:The study was conducted among 289 patients who were diagnosed with schizophrenia and were on treatment with risperidone (4–8 mg/day)-based therapy for a minimum of 4 weeks. Genotyping was carried by real-time quantitative polymerase chain reaction. All the patients were observed for the occurrences of ADRs during the study. Changes in prolactin levels and body weight were analyzed for a subgroup of 102 and 97 patients, respectively.Results:Risperidone-induced extrapyramidal symptoms (EPSs) were seen in 36.7% of patients. Among them, tremors were the most common symptom 31.8%. Risperidone-induced hyperprolactinemia and weight gain were seen in 87.2% and 53.6% in subgroup patients. Adverse effects such as sedation, gastrointestinal effects, and amenorrhea were seen in 9.7% (28/289), 5.1% (15/289), and 6.1% (7/114), respectively. Occurrence of DRD2 − 141 Ins/Del and Del/Del polymorphisms were significantly associated with increased prolactin levels in response to risperidone (odds ratio [OR] = 10.45; 95% confidence interval = 1.29–84.89, P = 0.004). No such association was observed with 5HTR2C (−759 C>T) polymorphism. Weight gain and EPS were not associated with the above genetic polymorphisms.Conclusion:Hyperprolactinemia, weight gain, and EPSs (>36.7%) were common adverse effects of risperidone. DRD2 – 141C Ins/Del and Del/Del polymorphisms were significantly associated with increased prolactin levels (OR = 10.45) in response to risperidone.

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“…While an association between some genetic polymorphisms85,86 and TD has been described in patients with schizophrenia, there is no consensus about a genetic predisposition to TD 87. On the other hand, several clinical variables have consistently predicted TD occurrence in schizophrenia in observational studies, RCTs, and reviews; these include anticholinergic medication; older age; intermittent antipsychotic treatment; high cumulative dose; higher negative, cognitive, and affective symptoms; and early movement side effects 88–91.…”

Section: Methodsmentioning

confidence: 99%

Safety, tolerability, and risks associated with first- and second-generation antipsychotics: a state-of-the-art clinical review

Solmi

Murru

Pacchiarotti

et al. 2017

TCRM

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Since the discovery of chlorpromazine (CPZ) in 1952, first-generation antipsychotics (FGAs) have revolutionized psychiatric care in terms of facilitating discharge from hospital and enabling large numbers of patients with severe mental illness (SMI) to be treated in the community. Second-generation antipsychotics (SGAs) ushered in a progressive shift from the paternalistic management of SMI symptoms to a patient-centered approach, which emphasized targets important to patients – psychosocial functioning, quality of life, and recovery. These drugs are no longer limited to specific Diagnostic and Statistical Manual of Mental Disorders (DSM) categories. Evidence indicates that SGAs show an improved safety and tolerability profile compared with FGAs. The incidence of treatment-emergent extrapyramidal side effects is lower, and there is less impairment of cognitive function and treatment-related negative symptoms. However, treatment with SGAs has been associated with a wide range of untoward effects, among which treatment-emergent weight gain and metabolic abnormalities are of notable concern. The present clinical review aims to summarize the safety and tolerability profile of selected FGAs and SGAs and to link treatment-related adverse effects to the pharmacodynamic profile of each drug. Evidence, predominantly derived from systematic reviews, meta-analyses, and clinical trials of the drugs amisulpride, aripiprazole, asenapine, brexpiprazole, cariprazine, clozapine, iloperidone, lurasidone, olanzapine, paliperidone, quetiapine, risperidone, sertindole, ziprasidone, CPZ, haloperidol, loxapine, and perphenazine, is summarized. In addition, the safety and tolerability profiles of antipsychotics are discussed in the context of the “behavioral toxicity” conceptual framework, which considers the longitudinal course and the clinical and therapeutic consequences of treatment-emergent side effects. In SMI, SGAs with safer metabolic profiles should ideally be prescribed first. However, alongside with safety, efficacy should also be considered on a patient-tailored basis.

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Pharmacogenetic study of antipsychotic induced acute extrapyramidal symptoms in a first episode psychosis cohort: role of dopamine, serotonin and glutamate candidate genes

Cited by 32 publications

References 49 publications

Improving pharmacogenetic prediction of extrapyramidal symptoms induced by antipsychotics

Improving pharmacogenetic prediction of extrapyramidal symptoms induced by antipsychotics

Risperidone-Induced Adverse Drug Reactions and Role of DRD2 (−141 C Ins/Del) and 5HTR2C (−759 C>T) Genetic Polymorphisms in Patients with Schizophrenia

Safety, tolerability, and risks associated with first- and second-generation antipsychotics: a state-of-the-art clinical review

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