Table 1 Baseline characteristics of the randomized controlled studies assessing the effect of pharmacogenomics testing guided in major depressive disorder patients

Bradley

12-week, prospective, subject- and rater-blind, multi-center

·age 19–87

·dianosed with depression and /or anxiety using the DSM-5 criteria of standard of care site procedures and verified by the MINI Psychiatic Interview

·HAM-D17 ≥ 18

NeuroIDgenetix

End-point PCR, real-time PCR, capillary electrophoresis

CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A4, CYP3A5, SLC6A4, [NM_001045.5:c.-1760 C > T], SLC6A4 [5-HTTLPR], COMT [NM_000754.3:c.472G > A], HTR2A [NM_000621.4:c.-998G > A], HTR2A [NM_000621.4:c.614e2211T > C], MTHFR [NM_005957.4:c.665 C > T], MTHFR [NM_005057.3:c.1286 A > C]

Guided group (n = 352): age 47.8 ± 14.5; female 73%;

Usual group (n = 333): age 47.3 ± 15.2; female 72%

Caucasian 63%, African-American 18%, Hispanic 17%, Asian 1%, other 1%

Fully

Greden

24-week, prospective, subject- and rater-blind, multi-center

·age > 18

·diagnosed with MDD (≥ 11 on the QIDS-C16 and self-rated QIDS-SR16 at screening and baseline)

·had an inadequate responseto at least one documented psychotropic treatment included on thepharmacogenomic test report within the current depressive episode

GeneSight

NA

CYP1A2, CYP2C9, CYP2C19, CYP3A4, CYP2B6, CYP2D6, HTR2A, SLC6A4

Guided group (n = 681): age 46.9 ± 14.5, female 71.8%;

Usual group (n = 717): age 48 ± 14.5, female 69.5%

White 80.6%, Black 14.9%, Asian 2.1%, other 2.4%

Partially

Han

8-week, subject-blind, multi-center

·age ≥ 20

·diagnosed with MDD according to DSM-5 criteria

·showed 3 or more on CGI-Improvement score despite of current antidepressant treatment with roper dosage at least 6 weeks or intolerance to current anti-depressant therapy based on clinicians’ judgement.

Neuropharmagen

NA

NA

Guided group (n = 52): age 44.2 ± 16.1, female 76.9%;

Usual group (n = 48): age 43.9 ± 13.8, female proportion 72.9%

Asian 100%

Partially

McCarthy

8-week, prospective, subject-blind, multi-center

·current depression in the context of Stage 1 or higher treatment-resistant depression

TaqMan-PCR (Pathway Genomics)

TaqMan-PCR

CYP1A2, CYP2C9, CYP2C19, CYP3A4, CYP3A5, CYP2B6, CYP2D6, HTR2A, SLC6A4, DRD2, HLARegion, 5HTTLPR, HTR2A, HTR2C, POLG, UGT1A4

Guided group (n = 75): age mean ± SEM 52.5 ± 1.5, female 21%;

Usual group (n = 74): age 50.3 ± 1.6, female 26%

NA

Partially

Oslin

24-week, prospective, rater-blind, pragmatic, multi-center

·receiving care at VA medical centers

·aged 18–80

·with a diagnosis of MDD

·a history of at least 1 treatment episode

·a plan to start a new episode of antidepressant monotherapy

·PHQ-9 > 9

GeneSight

NA

CYP1A, CYP2B6, CYP2C19, CYP2C9, CYP3A4, CYP2D6, UGT1A4, UGT2B15, SLC6A4, HTR2A, HLA-B*1502, HLA-A*3101

Guided group (n = 966): age 48 ± 15, female 24%;

Usual group (n = 978): age 47 ± 15, female 27%

White 69%, African American 18%, Asian Pacific Islander 3%, Native American 1%, other 9%

Partially

Perez

12-week, prospective, subject- and rater- blind, multi-center

·age ≥ 18

·with a principal diagnosis of MDD

·subjects with a clinician rated score in the CGI-S scale ≥ 4

·required medication de novo or were receiving treatment and required substitution or addition of drug treatment with an antidepressant drug

OpenArray

Real-time PCR, TaqMan-PCR

ABCB1, AKT1, BDNF, CACNG2, CES1, COMT, CRHR1, CYP1A2, CYP2B6, CYP2C19, CYP2C9, CYP2D6, CYP3A4, DDIT4, DRD3, EPHX1, FCHSD1, GRIK2, GRIK4, HLA-A, HTR1A, HTR2A, HTR2C, LPHN3, NEFM, OPRM1, RGS4, RPTOR, SLC6A4, UGT2B15

Guided group (n = 155): age 51.74 ± 12.05, female 63.9%;

Usual group (n = 161): age 50.74 ± 13.12, female 63.4%

Caucasian 92.40%, Latin American 5.38%, other 2.22%

Partially

Perlis

8-week, prospective, subject- and rater-blind, multi-center

·age 18–75

·with a primary diagnosis of nonpsychotic MDD based on DSM-5 criteria and MINI7.0, and HAM-D17 score > 18

·have failure of at least one prior adequate trial of a standard antidepressant for the current major depressive episode

Genecept Assay

NA

45 variants of 7 pharmacokinetic cytochrome P450 genes and 12 variants of 11 pharmacodynamic or other genes

Guided (n = 151): age 47.8 ± 12.38, female 70.9%;

Usual (n = 153): age 47.6 ± 12.06, female 72.5%

White 72.7%, African American 23.4%, Asian 0.3%, Native American 1%, Pacific Islander 1%, other 1.6%

Fully

Shan

8-week, prospective, subject-blind, single-center

·age 18–51

·at least a junior high school education level with the ability to understand survey contents

·HAM-D17 score ≥ 17 at baseline and the first item of the HAM-D17 (depressive mood) ≥ 2

·never received psychiatric treatment or have interrupted antidepressant medication for more than 2 weeks (fluoxetine for at least 4 weeks)

·with no psychotic symptoms

TaqMan probe–PCR

MassARRAY DNA

TaqMan probe-PCR, MALDI-TOF mass spectrometry

CYP2C19, CYP2D6, CYP1A2, SLC6A4, 5-HTR2A

Guided group (n = 31): age 26.52 ± 7.92, female proportion 19;

Unguided group (n = 40):

age 28.85 ± 8.93, female 65%

Asian

None

Singh

12-week, perspective, subject- and rater- blinded, single-center

·with a principal DSM-5 diagnosis of MDD

·HAM-D17 score > 18

CNSDose

PCR, MALDI-TOF mass spectrometry

ABCB1, ABCC1, CYP2D6, CYP2C19

Guided group (n = 74); mean age 44.2, male 42%;

Usual group (n = 74); mean age 44.3, male 39%

NA

Fully

Tiwari

52-week, prospective, patient- and rater-blinded, multi-center*

·age ≥ 18

·diagnosed with MDD according to DSM-4 criteria, QIDS-C16 score ≥ 11 at screening and baseline

·had inadequate response to at least one psychotropic medication included on the combinatorial pharmacogenomic report within the current depressive episode

GeneSight

Enhanced GeneSight

PCR, gel electrophoresis, xTAG assay

CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP3A4, HTR2A, SLC6A4, MC4R, CNR1, NPY, GCG, HCRTR2, NDUFS1

Guided group (n = 90): age 40.3 ± 15.3, female 65.6%;

Usual group (n = 93): age 42.3 ± 14.2, female 63.4%

Caucasian 84.1%, Asian 8.7%, Black 2.9%, Latin American 1.8%, other 2.5%

Partially

Winner

10-week, prospective subject-and rater-blind, single-center

·with a diagnosis of MDD or DDNOS were approached for enrollment by their treating clinician

·HAMD-17 score ≥ 14

GeneSight

Luminex xTAG

PCR

PCR, gel electrophoresis, xTAG assay

CYP2D6, CYP2C19, CYP1A2, SLC6A4, HTR2A

Guided group (n = 25): age 50.6 ± 14.6. female 69%;

Usual group (n = 24): age 47.8 ± 13.9. female 92%

Non-Hispanic White 98%, Black 2%

Fully