Influence of 5-HTR2A genetic polymorphisms on the efficacy of antidepressants in the treatment of major depressive disorder: A meta-analysis

Lin, Jianhao; Jiang, Mingyan; Kan, Zhoumi; Chu, Yang

doi:10.1016/j.jad.2014.06.012

Cited by 62 publications

(43 citation statements)

References 33 publications

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“…Several other studies investigated rs7997012 with negative results (Illi et al 2009;Kishi et al 2009;Perlis et al 2009;Uher et al 2009;Horstmann et al 2010), although none of these included samples as large as the STAR*D study. The effect of rs7997012 and rs6313 on antidepressant efficacy was confirmed by the most recent meta-analysis (Lin et al 2014).…”

Section: Genetic Polymorphisms Different Polymorphismsmentioning

confidence: 73%

Consensus paper of the WFSBP Task Force on Genetics: Genetics, epigenetics and gene expression markers of major depressive disorder and antidepressant response

Fabbri

Hosák

Mößner

et al. 2016

The World Journal of Biological Psychiatry

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Major depressive disorder (MDD) is a heritable disease with a heavy personal and socio-economic burden. Antidepressants of different classes are prescribed to treat MDD, but reliable and reproducible markers of efficacy are not available for clinical use. Further complicating treatment, the diagnosis of MDD is not guided by objective criteria, resulting in the risk of under-or overtreatment. A number of markers of MDD and antidepressant response have been investigated at the genetic, epigenetic, gene expression and protein levels. Polymorphisms in genes involved in anti-depressant metabolism (cytochrome P450 isoenzymes), antidepressant transport (ABCB1), glucocorticoid signalling (FKBP5) and serotonin neurotransmission (SLC6A4 and HTR2A) were among those included in the first pharmacogenetic assays that have been tested for clinical applicability. The results of these investigations were encouraging when examining patient-outcome improvement. Furthermore, a nine-serum biomarker panel (including BDNF, cortisol and soluble TNF-a receptor type II) showed good sensitivity and specificity in differentiating between MDD and healthy controls. These first diagnostic and response-predictive tests for MDD provided a source of optimism for future clinical applications. However, such findings should be considered very carefully because their benefit/cost ratio and clinical indications were not clearly demonstrated. Future tests may include combinations of different types of biomarkers and be specific for MDD subtypes or pathological dimensions.

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Section: Genetic Polymorphisms Different Polymorphismsmentioning

confidence: 73%

Consensus paper of the WFSBP Task Force on Genetics: Genetics, epigenetics and gene expression markers of major depressive disorder and antidepressant response

Fabbri

Hosák

Mößner

et al. 2016

The World Journal of Biological Psychiatry

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“…A multitude of studies have been conducted linking polymorphisms of the HTR2A gene with neuropsychiatric phenotypes, with contradictory findings [46]. A recent meta-analysis of studies involving polymorphisms of the gene and antidepressant treatment in major depression found significant association of rs7997012 G>A and rs6313 T>C with good responses to treatment with SSRIs or SNRIs in Caucasians, but no significant association in Asians [47]. Both polymorphisms are fairly common in Caucasians with frequencies of 35.6% for rs7997012 and 54.3% for rs6313; they are slightly less common in Asians with frequencies of 21.9% and 48.9% respectively.…”

Section: Htr2a and The Serotonin Signalmentioning

confidence: 99%

Pharmacogenetics of Antidepressants, A Review of Significant Genetic Variants in Different Populations

Reyes-Barron¹,

Tonarelli²,

Delozier³

et al. 2017

Clin Depress

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Major depressive disorder is a highly prevalent disease that is challenging to treat, often requiring medication and dose adjustments. Genetic factors play an important role in psychotropic medication responses. However, the translation of pharmacogenetics findings to clinical recommendations with regards to antidepressant responses is still in its early stages. We reviewed recent primary research articles, meta-analyses, and reviews on the pharmacogenetics of antidepressant treatment for major depressive disorder in different populations. We identified eight genes with likely associations with treatment responses and summarized genetic variants most likely to influence treatment responses. We determined the frequency of these variants in Caucasian, Asian, Hispanic, and African American populations. The genes are related to functions in drug metabolism, transport, signalling, stress response, and neuroplasticity. Clinical recommendations already exist for CYP2D6 and CYP2C19 cytochrome P450 drug metabolism genes. The other genes are: ABCB1 with single nucleotide polymorphisms (SNPs) rs2032583 and rs2235015; FKBP5 with SNPs rs1360780, rs3800373, and rs4713916; GNB3 with SNP rs5443; BDNF with SNP rs6265; HTR2A with SNPs rs7997012 and rs6313; and SLC6A4 with polymorphisms 5-HTTLPR and STin2. There is significant variability of the frequencies of these polymorphisms in the different populations we reviewed. There is also variability in the antidepressant responses between populations carrying the same polymorphism in some cases, indicating a likely polygenic influence. Future studies in the pharmacogenetics of antidepressants would benefit from including more subjects from underrepresented ethnic groups and stratifying results.

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“…However, if the patient was homozygous for the thymine polymorphism, the odds ratio increased to 1.85 (95% CI 1.18-2.90). Another variant, rs7997012, was associated with increased antidepressant response in patients carrying a guanine polymorphism (odds ratio 1.92, 95% CI 1.02-3.61) although with wider confidence interval the signal is not as strong 14. Patients carrying the guanine polymorphism also demonstrated better response to and tolerability of venlafaxine in the treatment of generalized anxiety disorder 15.…”

Section: Resultsmentioning

confidence: 99%

Overview of pharmacogenomic testing in clinical practice

Gross

Daniel

2018

Mental Health Clinician

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Introduction:Pharmacogenomic tests relevant to neuropsychiatric medications have been clinically available for more than a decade, but the utility of regular testing is still unknown. Tests available include both pharmacokinetic and pharmacodynamic targets. The potential practice benefits vary with each target.Methods:A 10-year literature review was completed utilizing the PubMed database to identify articles relating to the specific pharmacogenomic targets discussed. Further article selection was based on author review for clinical utility.Results:The clinical dosing guidance available for neuropsychiatric medications such as selective serotonin reuptake inhibitors and tricyclic antidepressants with varying genotypes is useful and has strong evidence to support testing, but it is limited to mainly pharmacokinetic application. Pharmacodynamic targets are gaining additional evidence with increased research, and although the mechanisms behind the potential interactions are scientifically sound, the bridge to clinical practice application is still lacking.Discussion:Although the benefits of decreasing adverse reactions and improving response time are appealing, clinicians may not utilize pharmacogenomic testing in routine practice due to several barriers. Further clinical guidance and studies are needed to support testing for other neuropsychiatric medications and targets.

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Influence of 5-HTR2A genetic polymorphisms on the efficacy of antidepressants in the treatment of major depressive disorder: A meta-analysis

Cited by 62 publications

References 33 publications

Consensus paper of the WFSBP Task Force on Genetics: Genetics, epigenetics and gene expression markers of major depressive disorder and antidepressant response

Consensus paper of the WFSBP Task Force on Genetics: Genetics, epigenetics and gene expression markers of major depressive disorder and antidepressant response

Pharmacogenetics of Antidepressants, A Review of Significant Genetic Variants in Different Populations

Overview of pharmacogenomic testing in clinical practice

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