The Progress and Pitfalls of Pharmacogenetics-Based Precision Medicine in Schizophrenia Spectrum Disorders: A Systematic Review and Meta-Analysis

The inadequate efficacy and adverse effects of antipsychotics severely affect the recovery of patients with schizophrenia spectrum disorders (SSD). We report the evidence for associations between pharmacogenetic (PGx) variants and antipsychotics outcomes, including antipsychotic response, antipsycho...

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Vydáno v:Journal of personalized medicine Ročník 13; číslo 3; s. 471
Hlavní autoři: Teng, Yuxin, Sandhu, Amrit, Liemburg, Edith J., Naderi, Elnaz, Alizadeh, Behrooz Z.
Médium: Journal Article
Jazyk:angličtina
Vydáno: Switzerland MDPI AG 04.03.2023
MDPI
Témata:
Antipsychotic drugs
Antipsychotics
Brain-derived neurotrophic factor
Clinical outcomes
Clozapine
Complications and side effects
CYP2D6 protein
Cytochrome P450
Decision making
Development and progression
Dopamine D1 receptors
Dopamine D2 receptors
Dopamine D3 receptors
Dopamine receptors
Drb1 protein
Drug therapy
Genetic aspects
Information sources
Mental disorders
Meta-analysis
Metabolic syndrome
Metabolism
Movement disorders
Neutropenia
Patient compliance
Pharmacogenetics
Pharmacokinetics
Phenotypes
Plasma levels
Precision medicine
Prolactin
Psychiatry
Psychotropic drugs
Schizophrenia
SNAP-25 protein
Systematic Review
Tardive dyskinesia
Netherlands
drug response
weigh-gain
personalized psychiatry
antipsychotics
pharmacokinetics
CYP
adverse events
schizophrenia
pharmacogenetics
tardive dyskinesia
ISSN:2075-4426, 2075-4426
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Shrnutí:The inadequate efficacy and adverse effects of antipsychotics severely affect the recovery of patients with schizophrenia spectrum disorders (SSD). We report the evidence for associations between pharmacogenetic (PGx) variants and antipsychotics outcomes, including antipsychotic response, antipsychotic-induced weight/BMI gain, metabolic syndrome, antipsychotic-related prolactin levels, antipsychotic-induced tardive dyskinesia (TD), clozapine-induced agranulocytosis (CLA), and drug concentration level (pharmacokinetics) in SSD patients. Through an in-depth systematic search in 2010–2022, we identified 501 records. We included 29 meta-analyses constituting pooled data from 298 original studies over 69 PGx variants across 39 genes, 4 metabolizing phenotypes of CYP2D9, and 3 of CYP2C19. We observed weak unadjusted nominal significant (p < 0.05) additive effects of PGx variants of DRD1, DRD2, DRD3, HTR1A, HTR2A, HTR3A, and COMT (10 variants) on antipsychotic response; DRD2, HTR2C, BDNF, ADRA2A, ADRB3, GNB3, INSIG2, LEP, MC4R, and SNAP25 (14 variants) on weight gain; HTR2C (one variant) on metabolic syndrome; DRD2 (one variant) on prolactin levels; COMT and BDNF (two variants) on TD; HLA-DRB1 (one variant) on CLA; CYP2D6 (four phenotypes) and CYP2C19 (two phenotypes) on antipsychotics plasma levels. In the future, well-designed longitudinal naturalistic multi-center PGx studies are needed to validate the effectiveness of PGx variants in antipsychotic outcomes before establishing any reproducible PGx passport in clinical practice.
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ISSN:2075-4426
2075-4426
DOI:10.3390/jpm13030471