Table 1.
Studies included in systematic review and meta‐analysis
| PMID | Title | Author and year | Trial registration | Study design | Sample size (n) | Primary end point (weeks) | Age, years | Female (%) | Ancestry (% European) | Eligibility | Baseline depressive symptom score/number of failed medications | Scale (remission definition) | Target genes | References |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 23,047,243 | Using a PGx algorithm to guide the treatment of depression | Hall‐Flavin 2012 | N/A | Open‐label, controlled | 44 | 8 | PGx = 43; TAU = 42 | PGx = 54; TAU = 54 | “The subjects almost exclusively identified themselves to be of European ancestry.” | 25–70 years MDD by DSM‐IV HAM‐D17 ≥ 14 baseline |
QIDS‐C16 PGx = 16.0; TAU = 15.4 PGx = 4.4; TAU = 4.4 |
HAM‐D17 (not reported) | CYP2D6, CYP2C19, CYP1A2, HTR2A, SLC6A4 | [22] |
| 24,018,772 | Utility of integrated PGx testing to support the treatment of MDD in a psychiatric outpatient setting | Hall‐Flavin 2013 | NCT01610063 | Open‐label, controlled | 165 | 8 | PGx = 41; TAU = 44 | PGx = 69; TAU = 77 | “…almost exclusively European ancestry of the participants, …” | 18–72 years MDD by DSM‐IV HAM‐D17 ≥ 14 baseline |
HAM‐D17 PGx = 23.0; TAU = 22.5 PGx = 3.6; TAU = 4.7 |
HAM‐D17 (≤ 7) | CYP2D6, CYP2C19, CYP1A2, HTR2A, SLC6A4 | [23] |
| 24,229,738 | A prospective, randomized, double‐blind study assessing the clinical impact of integrated pharmacogenomic testing for MDD | Winner 2013 | NCT01261364 | Blinded (participant & rater) RCT | 49 | 10 | PGx = 51; TAU = 48 | PGx = 69; TAU = 92 |
PGx = 96; TAU = 100 |
Age ≥ 18 years depression based on interview HAM‐D17 score ≥ 14 |
PGx = NA; TAU = NA PGx = 2.9; TAU = 2.7 |
HAM‐D17 (≤7) | CYP2D6, CYP2C19, CYP1A2, SLC6A4, HTR2A | [24] |
| 26,243,841 | Improved antidepressant remission in major depression via a Pharmacokinetic Pathway Polygene Pharmacogenetic Report | Singh 2015 | ACTRN12613001135707 | Blinded (participant & rater) RCT | 128 | 12 | PGx = 44; TAU = 44 | PGx = 58; TAU = 61 | PGx = 100; TAU = 100 | Age ≥ 18 years MDD by DSM‐V HAM‐D17 score ≥ 18 |
HAM‐D17 PGx = 24.8 TAU = 24.7 PGx = NA; TAU = NA |
HAM‐D17 (≤ 7) | CYP2C19, CYP2D6, UGT1A1 ABCB1, ABCC1 | [25] |
| 28,705,252 | Efficacy of prospective PGx testing in the treatment of MDD: results of a randomized, double‐blind clinical trial | Perez 2017 | NCT02529462 | Blinded (participant) RCT | 280 | 12 | PGx = 52; TAU = 51 | PGx = 64; TAU = 63 |
PGx = 91; TAU = 94 |
Age ≥ 18 years MDD by DSM‐IV‐TR CGI‐S ≥ 4 new to treatment or inadequately controlled |
HAM‐D17 PGx = 19.5; TAU = 19.0 PGx = NA; TAU = NA |
HAM‐D17 (≤7) | CYP1A2, CYP2B6, CYP2C19, CYP2C9, CYP2D6, CYP3A4, ABCB1, AKT1, BDNF, CACNG2, CES1, COMT, CRHR1, DDIT4, DRD3, EPHX1, FCHSD1, GRIK2, GRIK4, HLA‐A, HTR1A, HTR2A, HTR2C, LPHN3, NEFM, OPRM1, RGS4, RPTOR, SLC6A4, UGT2B15 | [26] |
| 28,992,526 | Improved efficacy with targeted PGx‐guided treatment of patients with depression and anxiety: A RCT demonstrating clinical utility | Bradley 2018 | NCT02878928 | Blinded (participant & rater) RCT | 93 | 8 | PGx = 48; TAU = 47 | PGx = 73; TAU = 72 |
PGx = 63; TAU = 63 |
19–87 years MDD and/or anxiety by DSM‐V New to treatment OR inadequately controlled |
HAM‐D17 PGx = 20; TAU = 20 PGx = NA; TAU = N/A |
HAM‐D17 (≤ 7) | CYP1A2, CYp2C9, CYP2C19, CYP2D6, CYP3A4, CYP3A5 SLC6A4, COMT, HTR2A, MTHFR | [27] |
| 30,466,219 | A PGx‐based antidepressant treatment for patients with MDD: Results from an 8‐week, Randomized, Single‐blinded Clinical Trial | Han 2018 | Not reported | Blinded (participant & rater) RCT | 100 | 8 | PGx = 44; TAU = 44 | PGx = 77; TAU = 73 |
PGx = 0; TAU = 0 |
Age > 20 years MDD by DSM‐V ≥ CGI‐3 OR intolerance to current medication |
QIDS‐C16 PGx = 24.5; TAU = 23.1 PGx = 2.5; TAU = 2.1 |
HAM‐D17 (≤ 7) | CYP1A2, CYP2B6, CYP2C19, CYP2C9, CYP2D6, CYP3A4, ABCB1, AKT1, BDNF, CACNG2, CES1, COMT, CRHR1, DDIT4, DRD3, EPHX1, FCHSD1, GRIK2, GRIK4, HLA‐A, HTR1A, HTR2A, HTR2C, LPHN3, NEFM, OPRM1, RGS4, RPTOR, SLC6A4, UGT2B15 | [28] |
| 30,677,646 | Impact of pharmacogenomics on clinical outcomes in MDD in the GUIDED trial: A large, patient‐ and rater‐blinded, randomized, controlled study | Greden 2019 | NCT02109939 | Blinded (participant & rater) RCT | 1,167 | 8 | PGx = 47; TAU = 48 | PGx = 72; TAU = 70 |
PGx = 79; TAU = 82 |
Age ≥ 18 years MDD by ≥11 on QIDS‐C16 Inadequate response |
HAM‐D17 PGx = 21.1; TAU = 21.4 PGx = 3.5; TAU = 3.5 |
HAM‐D17 (≤7) | CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A4, CYP2B6 SLC6A4, HTR2A | [29] |
| 31,572,113 | Preliminary Clinical Investigation of Combinatorial PGx Testing for the Optimized Treatment of Depression: A Randomized Single‐Blind Study | Shan 2019 | Not reported | Blinded (participant & rater) RCT | 71 | 8 | PGx = 27; TAU = 29 | PGx = 61; TAU = 65 |
PGx = 0; TAU = 0 |
Age 18–51 years MDD by DSM‐V HAM‐D17 ≥ 17 baseline Tx naive or free from medication for 2 weeks |
HAM‐D17 PGx = 21 TAU = 20.9 PGx = NA; TAU = NA |
HAM‐D17 (≤ 7) | CYP2C19, CYP2D6, CYP1A2 SLC6A4, HTR2A | [30] |
| 32,383,277 | Randomized, controlled, participant‐ and rater‐blind trial of PGx test‐guided treatment vs. treatment as usual for MDD | Perlis 2020 | NCT02634177 | Blinded (participant & rater) RCT | 296 | 8 | PGx = 48; TAU = 48 | PGx = 71; TAU = 73 |
PGx = 74; TAU = 72 |
Age ≥ 18 years MDD by DSM‐V > 18 SIGH‐D‐17 |
SIGH‐D‐17 PGx = 22.5; TAU = 22.1 PGx = 1.43 TAU = 1.52 |
SIGH‐D (≤ 7) | CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP3A4/5 SLC6A4, CACANA1C, ANK3, 5HT2C, MC4R, DRD2, COMT, ADRA2A, MTHFR, BDNF, OPRM1, GRIK1 | [31] |
| 33,938,307 | A prospective study to determine the clinical utility of PGx testing of veterans with treatment‐resistant depression | McCarthy 2021 | NCT04469322 | Blinded (participant) RCT | 102 | 8 | PGx = 52.5; TAU = 50.3 | PGx = 21; TAU = 24 |
PGx = 66; TAU = 69 |
Age ≥ 18 years veterans, MDD or Bipolar Depression Failed at least 1 medication |
QIDS‐SR PGx = 13.9; TAU = 13 PGx = NA; TAU = NA |
CGI (≤ 2) | CYP1A2, CYP2B6, CYP2C19, CYP2C9, CYP2D6, CYP3A4, CYP3A5, DRD2, HLA‐B, 5HTTLPR, HTR2A, HTR2C, POLG, SLC6A4, UGT1A4 | [32] |
| 35,288,545 | Clinical utility of combinatorial PGx testing in depression: A Canadian patient‐ and rater‐blinded, RCT | Tiwari 2022 | NCT02466477 | Blinded (participant & rater) RCT | 308 | 8 | PGx1 = 40; PGx2 = 41; TAU = 42 | PGx1 = 66; PGx2 = 65; TAU = 63 | PGx1 = 80; PGx2 = 83; TAU = 89 | Age ≥ 18 years MDD by DSM‐IV QIDS‐C16 ≥ 11 Inadequate response to at least 1 medication |
HAM‐D17 PGx 1 = 21.3; PGx2 = 21.5; TAU = 21.4 PGx 1 = 4; PGx2 = 3.7; TAU = 3 |
HAM‐D17 (≤ 7) | CYP1A2, CYP2B6, CYP2C19, CYP2C9, CYP2D6, CYP3A4 CNRI, GCG, HTR2A, HCRTR2, MC4R, NDUFS1, NPY, SLC6A4 | [34] |
| 35,819,423 |
Effect of PGx Testing for Drug‐Gene Interactions on Medication Selection and Remission of Symptoms in MDD The PRIME Care Randomized Clinical Trial |
Oslin 2022 | NCT03170362 | Open‐Label, controlled | 1944 | 24 | PGx = 48; TAU = 47 | PGx = 24; TAU = 27 |
PGx = 67 TAU = 70 |
Age 18–80 years, veterans, MDD, History of at least 1 treatment episode, plan to start new episode of antidepressant monotherapy, PHQ‐9 > 9. |
PHQ‐9 PGx = 17.5; TAU = 17.5 PGx = NA; TAU = NA |
PHQ‐9 (≤5) | CYP2D6, CYP2C19, CYP2C9, CYP2B6, CYP1A, CYP3A4, UDT1A4, UDT2B15, SLC6A4, HTR2A, HLA‐A, HLA‐B | [33] |
DSM‐IV, Diagnostic and Statistical Manual of Mental Disorders Fourth Edition; HAMD, Hamilton Rating Scale for Depression; MDD, major depression disorder; N/A, not applicable; PGx, pharmacogenomic; RCT, randomized controlled trial.