Antidepressant pharmacogenetics

Abstract

Early reports of clinical utility are published. The current evidence base for antidepressant pharmacogenetics is, however, not yet empirically robust enough to inform routine prescribing guidelines. Over the coming years, genetically guided versus unguided trials will help determine if antidepressant pharmacogenetics merits more widespread application.

The usefulness of genotyping cytochrome P450 enzymes in the treatment of depression

“…Both genome-wide association studies (GWASs), which assess millions of single nucleotide polymorphisms (SNPs), copy number variants, and other genetic variations, and candidate gene association studies, which investigate hundreds of a priori variants, examine a potential association of genotype with a broad phenotype such as treatment response [5]. A GWAS requires a much larger sample to maintain statistical power after adjustment for the probability of a type I error [5].…”

“…Indeed, of the 121 pharmacogenomic markers in the FDA's table of pharmacokinetic markers in drug labels, 26 are for psychiatric drugs [3,4]. A number of reviews of genetic testing in psychopharmacology have been published recently that address this possibility [3,5,6]. The present article addresses additional genetic studies of drug metabolism and adds additional dimensions of drug disposition and action at target sites.…”

Effect of desipramine on gene expression in the mouse frontal cortex – Microarray study

“…Despite extensive studies, the etiology of the disease or the mechanism of action of antidepressant drugs is still not clear. The meta-analyses carried out to date have identified some genes associated with depression or antidepressant drugs (especially the selective serotonin reuptake inhibitors) as putative biomarkers of the disease or therapy [1][2][3][4]. There were some genes connected with drug pharmacokinetics, the monoaminergic system, the stress hormone system, inflammation and neuroplasticity.…”

The Limitations of Genetic Testing in Psychiatry

“…Because treatment outcome seems to be influenced by multiple genetic polymorphisms, each with a small effect [3,21], research has moved toward analysis of networks of genes in the hope of developing more clinically useful information [42,43,44]. However, such studies have not produced clinically meaningful results [43,44].…”

“…However, such studies have not produced clinically meaningful results [43,44]. The Genome-Based Therapeutic Drugs for Depression (GENDEP; n = 811) study, a substudy of the Sequenced Treatment Alternatives to Relive Depression (STAR*D; n = 1,491) study, and the Munich Antidepressant Response Study (n = 339), did not find any combination of genetic markers that influenced treatment response in depression [1,44].…”