Pharmacogenetics of Antidepressants

Abstract

Up to 60% of depressed patients do not respond completely to antidepressants (ADs) and up to 30% do not respond at all. Genetic factors contribute for about 50% of the AD response. During the recent years the possible influence of a set of candidate genes as genetic predictors of AD response efficacy was investigated by us and others. They include the cytochrome P450 superfamily, the P-glycoprotein (ABCB1), the tryptophan hydroxylase, the catechol-Omethyltransferase, the monoamine oxidase A, the serotonin transporter (5-HTTLPR), the norepinephrine transporter, the dopamine transporter, variants in the 5-hydroxytryptamine receptors (5-HT1A, 5-HT2A, 5-HT3A, 5-HT3B, and 5-HT6), adrenoreceptor beta-1 and alpha-2, the dopamine receptors (D2), the G protein beta 3 subunit, the corticotropin releasing hormone receptors (CRHR1 and CRHR2), the glucocorticoid receptors, the c-AMP response-element binding, and the brain-derived neurotrophic factor. Marginal associations were reported for angiotensin I converting enzyme, circadian locomotor output cycles kaput protein, glutamatergic system, nitric oxide synthase, and interleukin 1-beta gene. In conclusion, gene variants seem to influence human behavior, liability to disorders and treatment response. Nonetheless, gene × environment interactions have been hypothesized to modulate several of these effects.

Biological Alterations in Depression

“…Genes that confer risk to depression have been primarily identified using candidate gene analysis approaches, while recent efforts to uncover genetic markers of antidepressant response include the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial and Genome-Based Therapeutic Drugs for Depression (GENDEP) study, which looked at genome-wide associations of common variants with antidepressant response. Genetic studies of depression (Levinson, 2006;Lohoff, 2010;Shyn & Hamilton, 2010) and antidepressant response (Crisafulli et al, 2011;Kato & Serretti, 2010;Porcelli et al, 2010) are reviewed in this chapter with a focus on several genes.…”

Pharmacogenetics of antidepressant drugs: An update

“…So far, most pharmacogenetics studies have investigated genes involved in the pharmacokinetics and pharmacodynamics of ADs [15]. Several genetic variations at level of drug metabolizing enzymes, drug transporters, drug targets and other biomarker genes, possibly influencing clinical response, have been identified [15]. Present article will update the major findings related to the pharmacogenetics of genes affecting the response to ADs.…”

“…Pharmacogenetic studies suggest that single nucleotide polymorphisms (SNPs) can be used in clinical association studies to determine the contribution of genetic variance in drug response. Moreover, associating novel candidate genes with antidepressant response may lead to the development of a new class of medications [13,14,15]. In recent years, the development of pharmacogenetics has provided more opportunities for individualized pharmacotherapy of depressive disorders [15].…”

“…Moreover, associating novel candidate genes with antidepressant response may lead to the development of a new class of medications [13,14,15]. In recent years, the development of pharmacogenetics has provided more opportunities for individualized pharmacotherapy of depressive disorders [15]. So far, most pharmacogenetics studies have investigated genes involved in the pharmacokinetics and pharmacodynamics of ADs [15].…”

“…In recent years, the development of pharmacogenetics has provided more opportunities for individualized pharmacotherapy of depressive disorders [15]. So far, most pharmacogenetics studies have investigated genes involved in the pharmacokinetics and pharmacodynamics of ADs [15]. Several genetic variations at level of drug metabolizing enzymes, drug transporters, drug targets and other biomarker genes, possibly influencing clinical response, have been identified [15].…”