Review of evidence for genetic testing for CYP450 polymorphisms in management of patients with nonpsychotic depression with selective serotonin reuptake inhibitors.
OBJECTIVE
Cytochrome P450 (CYP450) enzymes metabolize selective serotonin reuptake inhibitor (SSRI) drugs used in treatment of depression. Variants in these genes may impact treatment efficacy and tolerability. The purpose of this study was 2-fold: to systematically review the literature for evidence supporting CYP450 genotyping to guide SSRI treatment for major depression, and, where evidence is inadequate, to suggest future research.


METHODS
We searched MEDLINE(R) and other databases for studies addressing five key questions suggested by the Evaluation of Genomic Applications in Practice and Prevention Working Group. Eligibility criteria were defined, and studies were reviewed independently by paired researchers. A conceptual model was developed to guide future research.


RESULTS
Review of 1200 abstracts led to the final inclusion of 37 articles. The evidence indicates relatively high analytic sensitivity and specificity of tests detecting a subset of polymorphisms of CYP2D6, 2C19, 2C8, 2C9, and 1A1. We found marginal evidence regarding a clinical association between CYP450 variants and SSRI metabolism, efficacy, and tolerability in the treatment of depression.


CONCLUSIONS
Current evidence does not support the use of CYP450 genotyping to guide SSRI treatment of patients with depression. Studies are proposed that will effectively guide decision-making in the area of CYP450 testing in depression, and genetic testing more generally.
Thakur
Mugdha
M
Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, North Carolina 27710, USA. thaku001@mc.duke.edu
Grossman
Iris
I
McCrory
Douglas C
DC
Orlando
Lori A
LA
Steffens
David C
DC
Cline
Kathryn E
KE
Gray
Rebecca N
RN
Farmer
Jennifer
J
DeJesus
Georgette
G
O'Brien
Cara
C
Samsa
Gregory
G
Goldstein
David B
DB
Matchar
David B
DB
D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D003866:Depressive Disorder / Q000188:drug therapy* / Q000235:genetics; D019317:Evidence-Based Medicine; D005820:Genetic Testing; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D016239:MEDLINE; D011110:Polymorphism, Genetic; D015203:Reproducibility of Results; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*
D003577:Cytochrome P-450 Enzyme System; D017367:Selective Serotonin Reuptake Inhibitors