The pharmacogenetics of the new-generation antipsychotics – A scoping review focused on patients with severe psychiatric disorders

Vasiliu, O.

doi:10.3389/fpsyt.2023.1124796

Cited by 9 publications

(8 citation statements)

References 95 publications

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“…Differences in pharmacokinetics and pharmacodynamics of brexpiprazole due to possible impact of gene variability requires further exploration. Unfortunately, however, data on the impact of genetic variations on brexpiprazole pharmacodynamics and tolerability are still limited 37 …”

Section: Discussionmentioning

confidence: 99%

“…Unfortunately, however, data on the impact of genetic variations on brexpiprazole pharmacodynamics and tolerability are still limited. 37 Despite their widespread use, attention to potential tolerability issues other than akathisia is important when considering using antipsychotic medication in patients with MDD. 38 Extrapyramidal symptoms, metabolic syndrome effects, increased prolactin levels, and subjective negative experiences such as insomnia are particularly important to consider.…”

Section: Pcn Psychiatry Andmentioning

confidence: 99%

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Adjunctive brexpiprazole 1 mg and 2 mg daily for Japanese patients with major depressive disorder following inadequate response to antidepressants: a phase 2/3, randomized, double‐blind (BLESS) study

Kato,

Shiosakai,

Kuwahara

et al. 2023

Psychiatry Clin Neurosci

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AimsInadequate antidepressant response interrupts effective treatment of major depressive disorder (MDD). The BLESS study evaluates the dosage, efficacy, and safety of brexpiprazole adjunctive therapy in Japanese patients with inadequate antidepressant therapy (ADT) response.MethodsThis placebo‐controlled, randomized, multicenter, parallel‐group phase 2/3 study randomized Japanese MDD patients (Hamilton Rating Scale for Depression 17‐item total score ≥ 14; historical inadequate response to 1–3 ADTs) with inadequate response to 8‐week single‐blind, prospective SSRI/SNRI treatment to 6‐week adjunctive treatment with brexpiprazole 1 mg, 2 mg, or placebo. The primary endpoint was change in Montgomery‐Åsberg Depression Rating Scale (MADRS) total score from baseline. Secondary endpoints included MADRS response, remission rate, and Clinical Global Impression‐Improvement score. Safety was comprehensively evaluated, especially regarding antipsychotic adverse events (AEs).ResultsOf 1194 screened patients, 740 were randomized and 736 (1 mg, n = 248; 2 mg, n = 245; placebo, n = 243) had ≥1 baseline/post‐baseline MADRS total score. The LSM (SE) change from baseline in MADRS total score at Week 6 by MMRM analysis was −8.5 (0.47) with brexpiprazole 1 mg, −8.2 (0.47) with brexpiprazole 2 mg, and −6.7 (0.47) with placebo (placebo‐adjusted LSM difference [95% CI]: 1 mg, −1.7 [−3.0, −0.4]; P = 0.0089; 2 mg, −1.4 [−2.7, −0.1]; P = 0.0312). Secondary efficacy results supported the primary endpoint. Brexpiprazole was generally well tolerated.ConclusionBrexpiprazole 1 mg daily was an appropriate starting dose and both 1 mg and 2 mg daily were effective and well tolerated as adjunctive therapy for Japanese MDD patients not adequately responsive to ADT.

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Section: Discussionmentioning

confidence: 99%

Section: Pcn Psychiatry Andmentioning

confidence: 99%

Adjunctive brexpiprazole 1 mg and 2 mg daily for Japanese patients with major depressive disorder following inadequate response to antidepressants: a phase 2/3, randomized, double‐blind (BLESS) study

Kato,

Shiosakai,

Kuwahara

et al. 2023

Psychiatry Clin Neurosci

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“…Currently, antipsychotic medications are the primary treatment modality for schizophrenia. Certain clinical studies indicate that the combination of antipsychotic drugs with nonsteroidal anti-inflammatory drugs and anti-inflammatory agents can ameliorate symptoms in individuals with schizophrenia ( 39 ). Over time, research has revealed intricate connections between the immune system, inflammation, and alterations in mood, cognition, and behavior.…”

Section: Discussionmentioning

confidence: 99%

Correlations between schizophrenia and lichen planus: a two-sample bidirectional Mendelian randomization study

Chen,

Fu,

et al. 2023

Front. Psychiatry

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BackgroundSeveral existing studies have shown a correlation between schizophrenia and lichen planus (LP). However, the causality of this relationship remains uncertain. Thus, this study aimed to examine the causal association between schizophrenia and LP.MethodsA two-sample Mendelian randomization (MR) study was carried out to investigate whether schizophrenia is causally related to LP and vice versa, and genetic variants in this study were taken from previous genome-wide association studies. We used the inverse variance weighted (IVW) method as the main analysis. Furthermore, several sensitivity analyses were performed to assess heterogeneity, horizontal pleiotropy, and stability.ResultsOur results show that schizophrenia has a protective effect on LP (OR = 0.881, 95%CI = 0.795–0.975, p = 0.015). Conversely, we observed no significant relationship between LP and schizophrenia in reverse MR analysis (OR = 0.934, 95%CI = 0.851–1.026, p = 0.156).ConclusionOur two-sample Mendelian randomization study supports a significant causal relationship between LP and schizophrenia and finds that schizophrenia can reduce the incidence of LP. This is in contrast to previous findings and provides new insights into the relationship between LP and schizophrenia, but the exact mechanism needs further investigation.

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“…Articles were excluded from this revision for the following reasons: (1) not drug of interest (not antipsychotics); (2) other areas of research (Alzheimer disease, depression, implementation of informatic tools, etc. ); (3) not original new data (reviews of publications); (4) case-report studies; (5) studies with exclusive pharmacokinetic design and outcomes; (6) studies with not reported response phenotype. A total of 269 relevant papers were identified that reported original pharmacogenetic or pharmacogenomic results on a variety of antipsychotic response phenotypes (influence of genetic variants on treatment response, adverse reactions and/or drug clearance).…”

Section: Literature Reviewmentioning

confidence: 99%

“…At present, the implementation of pharmacogenetic interventions in psychiatric settings is very limited, and further proof of their clinical utility is required. Pharmacogenomic research conducted in the last decade has advanced our knowledge on the mechanism of action of antipsychotic drugs by confirming the therapeutic value of known targets [ 2 , 6 ]. Further research into genomic and epigenomic factors contributing to response may help to improve the accuracy and clinical applicability of genetic information in psychiatry.…”

Section: Introductionmentioning

confidence: 99%

Clinical Utility and Implementation of Pharmacogenomics for the Personalisation of Antipsychotic Treatments

Hernandez,

Cullell,

Cendros

et al. 2024

Pharmaceutics

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Decades of pharmacogenetic research have revealed genetic biomarkers of clinical response to antipsychotics. Genetic variants in antipsychotic targets, dopamine and serotonin receptors in particular, and in metabolic enzymes have been associated with the efficacy and toxicity of antipsychotic treatments. However, genetic prediction of antipsychotic response based on these biomarkers is far from accurate. Despite the clinical validity of these findings, the clinical utility remains unclear. Nevertheless, genetic information on CYP metabolic enzymes responsible for the biotransformation of most commercially available antipsychotics has proven to be effective for the personalisation of clinical dosing, resulting in a reduction of induced side effects and in an increase in efficacy. However, pharmacogenetic information is rarely used in psychiatric settings as a prescription aid. Lack of studies on cost-effectiveness, absence of clinical guidelines based on pharmacogenetic biomarkers for several commonly used antipsychotics, the cost of genetic testing and the delay in results delivery hamper the implementation of pharmacogenetic interventions in clinical settings. This narrative review will comment on the existing pharmacogenetic information, the clinical utility of pharmacogenetic findings, and their current and future implementations.

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The pharmacogenetics of the new-generation antipsychotics – A scoping review focused on patients with severe psychiatric disorders

Cited by 9 publications

References 95 publications

Adjunctive brexpiprazole 1 mg and 2 mg daily for Japanese patients with major depressive disorder following inadequate response to antidepressants: a phase 2/3, randomized, double‐blind (BLESS) study

Adjunctive brexpiprazole 1 mg and 2 mg daily for Japanese patients with major depressive disorder following inadequate response to antidepressants: a phase 2/3, randomized, double‐blind (BLESS) study

Correlations between schizophrenia and lichen planus: a two-sample bidirectional Mendelian randomization study

Clinical Utility and Implementation of Pharmacogenomics for the Personalisation of Antipsychotic Treatments

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