Cytochrome P450 CYP1A2, CYP2C9, CYP2C19 and CYP2D6 genes are not associated with response and remission in a sample of depressive patients

Abstract

Cytochrome P450 genes are involved in the metabolism of antidepressants and could influence treatment response. The aim of this study was to investigate the role of allelic variations of the cytochrome P450 CYP1A2, CYP2C9, CYP2C19 and CYP2D6 genes in antidepressant treatment response and remission rates. Two hundred and seventy-eight patients affected by major depression, responders (N = 81) and nonresponders (N=197) to at least one adequate antidepressant treatment, were recruited with a multicentre design for resistant depression and genotyped for all relevant variations. None of the considered metabolic profiles (e.g. poor, intermediate, extensive and ultrarapid metabolizers) was found to be associated with either response or remission rates. In conclusion, the investigated cytochrome genes do not seem to play a major role in antidepressant response in the present sample of depressive patients. Nevertheless, methodological and sample size limitations of this study do not allow definitive conclusions.

Response to CYP2D6 substrate antidepressants is predicted by a CYP2D6 composite phenotype based on genotype and comedications with CYP2D6 inhibitors

“…For example, a lower antidepressant response or remission is reported for UMg and PMg (Kawanishi et al 2004;Tsai et al 2010;Rau et al 2004). However, several studies failed to report such an association: with fluvoxamine (Gerstenberg et al 2003;Ohara et al 2003); with citalopram (Peters et al 2008;Mrazek et al 2011);with paroxetine (Gex-Fabry et al 2008); with paroxetine and mirtazapine (Murphy et al 2003); with fluoxetine and nortriptyline (Roberts et al 2004); with escitalopram and nortriptyline (Hodgson et al 2014); with several antidepressants (Grasmader et al 2004;Serretti et al 2009). …”

Pharmacogenetics of antidepressant response

“…However, pharmacokinetic variations may selectively influence dosing, although, as we recently confirmed, for drugs with a relatively large therapeutic range the impact may be minimal. 49 Moreover, several confounding factors need to be considered in pharmacokinetic studies that may explain previously controversial findings. A single drug is metabolized by specific enzymes, but the result of this product may be an active molecule that can be metabolized by a different enzyme.…”

Failure to Replicate Influence of GRIK4 and GNB3 Polymorphisms on Treatment Outcome in Major Depression

“…A detailed description of the whole sample has been reported elsewhere [18] . Here, we present data on a subsample of patients for whom genetic data of GRIK4 and GNB3 were available and who had previously been investigated for cytochrome and CREB1 variants [19,20] . A sample of 76 healthy control subjects collected in the Erasme Hospital and clinically screened for absence of psychiatric disorders was also included in order to investigate possible differences in terms of genotypic and allelic frequencies between MDD patients and healthy subjects.…”