Effect of Pharmacogenetic-Based Decision Support Tools in Improving Depression Outcomes: A Systematic Review

Figures & data

Figure 1 Flow diagram of selection process.

Table 1 Description of Pharmacogenetic Tests

Test	Manufacturer	Eligibility	Genes	Medications
GeneSight Psychotropic^Citation57	Assurex Health, Inc, Mason, OH, USA	Patients with depression	56 alleles and variants across 12 genes: 8 Pharmacokinetic genes: CYP2D6, CYP2C19, CYP2C9, CYP3A4, CYP2B6, CYP1A2, UGT1A4, UGT2B15 4 Pharmacodynamic genes: SLC6A4, HTR2A, HLA-A*3101, HLA-B*1502	57 psychotropic medications
Genecept Assay^Citation58	Dynacare, Inc, Brampton, Ontario, Canada	Patients with psychiatric and medical morbidities, patients with suboptimal response, patients with polypharmacy, and patients with medication adherence issues	18 genes: 6 Pharmacokinetic genes: CYP2C19, CYP2C9, CYP2D6, CYP2B6, CYP1A2, CYP3A4/5 12 Pharmacodynamic genes: SLC6A4, CACNA1C, ANK3, 5HT2C, MC4R, DRD2, COMT, ADRA2A, MTHFR, BDNF, OPRM1, GRIK1	Not specified
CNSDose^Citation59	CNSDose, Melbourne, Victoria, Australia	Patients with psychiatric disorders, patients with general medical conditions, patients with polypharmacy, and patients with depression and co-occurring conditions	Liver and brain genes: ABCB1, ABCC1, CYP2C19, CYP2D6, UGT1A1	Antipsychotics, anxiolytics, mood stabilizers, hypnotics, ADHD, Alzheimer’s, cardiology, endocrinology, pain medicines, gastroenterology medicines
Neuropharmagen^Citation60	AB-Biotics SA, Barcelona, Spain	Patients with psychiatric disorders	25 genes: 10 Pharmacokinetic genes: CYP2C19, CYP2C9, CYP2D6, CYP2B6, CYP1A2, CYP3A4, ABCB1, CES1, EPHX1, UGT2B15 15 Pharmacodynamic genes: SLC6A4, COMT, BDNF, OPRM1, GRIK2, GRIK4, AKT1, AL157359, DDIT4, FCHSD1, HLA-A, HTR2A, HTR2C, LPHN3, RPTOR	59 psychotropic medications
Amplichip CYP450 Test^Citation61	Roche Molecular Systems, Basel, Switzerland	Patients receiving CYP2D6 and CYP2C19 substrates	2 Pharmacokinetic genes: CYP2D6, CYP2C19	CYP2D6 and CYP2C19 substrates
NeuroIDgenetix^Citation62	AltheaDx, Inc, San Diego, CA, USA	Patients with depression and anxiety	10 genes: 6 Pharmacokinetic genes: CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A4, CYP3A5 4 Pharmacodynamic genes: SLC6A4, COMT, HTR2A, MTHFR	Approx. 40 psychotropic medications
GeneLex^Citation63	GeneLex, Seattle, WA, USA	Patients with depression, patients with epilepsy, patients with general medical conditions, patients with cancer, and patients with polypharmacy	25 genes: 8 Pharmacokinetic genes: CYP2C9, CYP2C19, CYP2D6, CYP3A4/CYP3A5, CYP1A2, CYP2B6, CYP4F2 17 Pharmacodynamic genes: ADRA2A, COMT, DPYD, Factor II–Factor V, Leiden, GRIK4, HLA-A or HLA-B, HTR2A, HTR2C, IFNL3, MTHFR, NAT2, OPRM1, SLCO1B1, TPMT, UGT1A1	Not specified
HILOmet^Citation64	Rennova Health, Inc, West Palm Beach, FL, USA	Patients with treatment resistance or drug intolerance to neuropsychiatric or cardiometabolic drugs	3 Pharmacokinetic genes: CYP2D6, CYP2C9, CYP2C19	Not specified
Pillcheck^Citation65	GeneYouIn Inc, North York, Canada	Patients with psychiatric disorders, patients with cardiovascular and gastroenterology medical conditions, patients taking analgesics, refractory patients, patients undergoing surgery and who will be prescribed analgesics during recovery, patients starting treatment for chronic conditions	19 genes: 8 Pharmacokinetic genes: CYP2D6, CYP2C19, CYP2C9, CYP3A4/A5, CYP1A2, CYP2C8, CYP2B6 11 Pharmacodynamic genes: OPRM1, SLCO1B1, VKORC1, DPYD, F2, F5, IFNL3, TPMT, UGT1A1, UGT2B15, ADRB2	205 medications

Table 2 Characteristics of Eligible Systematic Reviews

Study	Aim	Search Strategy	Population	Intervention	Comparator	Outcomes	Included Studies
Health Quality Ontario^Citation24	To assess the effect of GeneSight test compared to TAU	Timeline: Until February 2016 Databases: >2 Search terms: Provided Flow diagram: Available Limits: English only Test: GeneSight	Depression, GAD, psychiatric patients (n=13,377)	PGX-guided treatment with GeneSight	Unguided treatment	Primary outcomes: Prevention of suicide, remission, response, depression score, quality of life, efficacy Secondary outcomes: Impact on therapeutic decisions, patient and clinician satisfaction	2 Non-randomized open-label studies 1 RCT 1 propensity score cohort
Bousman et al^Citation23	To examine the remission rates of 2nd generation PGX-guided treatment in MDD patients	Timeline: Until May 2018 Databases: >2 Search terms: Provided Limits: English only Flow diagram: Available Test: Not specified	Adults with but not limited to severe or uncontrolled depression (n=1737)	PGX-guided treatment	Unguided treatment	Remission	5 RCTs: 2 GeneSight, 1 Neuropharmagen, 1 CNSDose, 1 NeuroIDgenetix
Fabbri et al^Citation25	To provide an update on the currently available PGx tests for predicting treatment outcomes of drugs for depression with quality evaluation for each available study	Timeline: Until January 2018 Databases: >2 Search terms: Provided Limits: English only Flow diagram: Available Test: Not specified	Not clearly defined, but patients with depression (n=not available)	PGX-guided treatment	Unguided treatment	Safety and efficacy	6 RCTs: GeneSight, CNSDose, Neuropharmagen, NeuroIDgenetix, Genelex, academic study based on FKBP5 SNPs 6 case–control non- RCTs: 3 GeneSight, Genecept, GeneLex, academic study based on ABCB1 SNPs 9 observational studies 2 AmpliChip, CNSDose GeneSight, Genecept, Genelex, HILOmet, Neuropharmagen, Pillcheck
Rosenblat et al^Citation26	To determine the effect of PGX-guided treatment on response and remission rates in the acute treatment of MDD as compared to unguided treatment	Timeline: Until December 2017 Databases: 2 Search terms: Provided Limits: Human studies, English only Flow diagram: Available Test: Not specified	Patients with MDD (n=not available)	PGX-guided treatment	Unguided treatment	Response and remission	4 RCTs: GeneSight, CNSDOse, Neuropharmagen, NeuroIDgenetix 2 Unblinded, open-label cohort studies 2 GeneSight
Rosenblat et al^Citation27	To determine the effect of PGX testing on clinical outcomes in MDD and assess its cost-effectiveness	Timeline: Until October 2015 Databases: 2 Search terms: Provided Limits: English only Flow diagram: Available Test: Not specified	Patients with MDD (n=not available)	Guided treatment	Unguided treatment	Efficacy, cost effectiveness	2 case–control non- RCTs: 2 GeneSight 2 RCTs: GeneSight, CNSDose 1 Observational: Genecept
Brown et al^Citation28	To assess the clinical utility of the combinatorial test GeneSight in patients with MDD	Timeline: Not available. Database: 1 Search terms: Provided. Limits: N/A Flow diagram: Available Test: GeneSight	Patients with MDD with prior medication failure (n=1556)	Guided treatment with GeneSight	Unguided treatment	Symptoms improvement, response, remission	2 RCTs 2 Open- label trials 1 Pooled analysis

Abbreviations: PGX, pharmacogenetic; TAU, treatment as usual; MDD, major depressive disorder; RCT, randomized controlled trial; GAD, generalized anxiety disorder.

Table 3 Characteristics of Eligible Randomized Controlled Trials (RCTs)

Study	Aim	Study Design	Sample Size	Eligibility Criteria	Population
Han et al^Citation29	To evaluate the effectiveness and tolerability of commercial PGX test Neuropharmagen vs TAU in the Korean population	Randomization: Stratified by study center with a 1:1 ratio Blinding: Single blinded Duration: 8 weeks Tool: Neuropharmagen Main outcomes: Primary outcomes: The mean change of scale (HAMD-17) from baseline to end of treatment. The change of total score of FIBSER from baseline to end of treatment was the co-primary endpoint Secondary outcomes: Response as reduction in HAMD-17 total score of at least 50% from baseline. Remission was defined as an absolute HAMD-17 total score of ≥7 at the end of treatment Other secondary endpoints: Changes in (PHQ-9/15), (CGI-S) score, (GAD-7) total score, and SDS	100	Inclusion criteria 1) At least 20 years old 2) Diagnosis of MDD according to DSM-5 criteria 3) CGI-S score ≥3 4) Intolerance to current antidepressant therapy Exclusion criteria 1) Not currently on antidepressant treatment 2) Pregnancy or nursing 3) Substance abuse within the past 12 months 4) Diagnosed with unstable medical or neurological disorders 8) Had formal cognitive–behavioral therapy 9) Participated in a clinical trial within the past month 10) Hospitalized or had ECT within 8 weeks	Groups: Guided (n=52), TAU (n=48) Age: 44 vs 43 years Sex: 77% female Ethnicity: Not reported Depression status: Moderate-to-severe MDD symptoms measured by HAMD-17 total scores (23.8±4.8). All the patients had a history of at least two previous failed antidepressant treatments for current MDD
Greden et al^Citation30	To evaluate the utility of PGX testing in patients with MDD Data are presented from the Genomics Used to Improve DEpression Decisions (GUIDED) trial	Randomization: 1:1 to guided or TAU Blinding: Patient- and rater-blinded Duration: Symptom improvement, response, and remission were monitored over 24 weeks with the primary endpoint at week 8 Tool: GeneSight Main outcomes: Assessed at baseline, week 4, week 8, week 12, and week 24 Primary outcome: Change in HAMD-17 Secondary outcome: Response and remission at week 8 according to HAMD-17, QIDS-C16, and PHQ-9, and side effects	1541 patients were included in the final intent-to-treat cohort 1398 patients were included in per-protocol cohort	Inclusion criteria 1) Over the age of 18 2) Diagnosed with MDD (≥11 on the QIDS-C16 and self-rated QIDS-SR16 at screening and baseline) 3) Had an inadequate response to at least one psychotropic treatment Exclusion criteria 1) Had significant suicidal risk 2) Severe co-occurring psychiatric or cognitive disorders, cognitive disorders and/or unstable or significant medical conditions	Outpatients from 60 academic and community sites in the USA Groups: In the per-protocol cohort, 607 patients in TAU, 560 patients in the guided arm Age: Mean 47.5 years Sex: 71% female Ethnicity: 92.1% non-Hispanic non-Latino, 80.6% white Depression status: Moderate (392/1398, 28.0%), severe (493/1398, 35.3%), or very severe (513/1398, 36.7%)
Thase et al^Citation31	To evaluate the extent to which PGX positively influenced antidepressant outcomes in patients entering the GUIDED trial taking medications subject to gene–drug interactions	Randomization: 1:1 to guided treatment or TAU Blinding: Patient- and rater-blinded Duration: 8 weeks Tool: GeneSight Main outcomes: Assessed at baseline, week 4, week 8, week 12, and week 24. Outcomes assessed at week 8 included % change in HAMD-17 score from baseline. Response (≥50% decrease in HAMD-17 score). Remission (HAMD-17 score ≤7) Same outcomes were evaluated in patients whose medications were switched from baseline to week 8	912 patients, Guided (n= 439), TAU (n=473)	Same as Greden et al,^Citation30 but included mainly patients who were taking medications subject to gene–drug interactions at baseline (“use with caution” and “use with increased caution and with more frequent monitoring” report categories)	Same as Greden et al^Citation30

Abbreviations: PGX, pharmacogenetic; TAU, treatment as usual; MDD, major depressive disorder; DSM-5, Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition; GAD-7, Generalized Anxiety Disorder 7-item; CGI-S, Clinical Global Impression Scale; HAMD-17, 17-item Hamilton Depression Rating Scale; PHQ-9, Patient Health Questionnaire-9; QIDS-C16, Clinician-rated Quick Inventory of Depressive Symptomatology; QIDS-SR16, Self-Rated Quick Inventory of Depressive Symptomatology; FIBSER, Frequency, Intensity, and Burden of Side Effects Rating; SDS, Sheehan Disability Scale; ECT, electroconvulsive therapy.

Table 4 Safety and Efficacy Results of Eligible Studies

Study	Safety	Efficacy	Authors' Conclusion
Systematic reviews
Health Quality Ontario^Citation24	N/A	Depression score: Patients who received guided care had a greater reduction in depression at 8 weeks but not 10 weeks (RCT) on HAMD, QIDS-C16, and PHQ-9 Response: A greater proportion of patients had a response to depression therapy with GeneSight-guided care than those who received usual care Remission: There was a statistically significant benefit for the GeneSight guided group on QIDS-C16, but no significant difference on HAMD-17 or PHQ-9	Patients who received GeneSight-guided medication had improved response and greater improvement in measures of depression but no observed differences in rates of remission, based on low to very low confidence in the evidence
Bousman et al^Citation23	N/A	Remission: (RR=1.71, 95% CI: 1.17–2.48, p= 0.005) in favor of guided group Two trials, Singh and Perez et al, were identified as influential studies. Removal of the Singh trial resulted in a trend-level pooled RR of 1.46 (95% CI: 0.99–2.16, p=0.056), whereas removal of the Perez et al trial produced an increased pooled RR of 1.98 (95% CI: 1.47–2.66, p<0.001)	This article serves as a “tipping point” of evidence in support of PGX-guided antidepressant treatment, in the context of moderate to severe depression
Fabbri et al^Citation25	Better tolerability, lower rehospitalization and emergency room visits in the guided group	RCT results: Higher response rates and remission in the guided group Case–control non-RCTs: Compared to TAU, patients had higher response and remission rates, and percent symptom improvement Meta-analysis of three GeneSight studies: No improvement in remission rate but better response rate and symptom improvement Observational studies: In one study all subjects were genotyped using Neuropharmagen, and patients whose treatment followed the PGX report showed a higher chance of symptom improvement	Relatively weak clinical benefits were reported by RCTs and higher clinical benefits by non-RCTs, but with greater risk of bias
Rosenblat et al^Citation26	N/A	Response rate: Subgrouping by genetic test showed significant differences with some genetic tests (NeuroIDgenetix),(GeneSight, Neuropharmagen) showed no significant difference between PGX-guided and unguided treatment, and CNSDose was not included in this analysis. One study was influential, and did not appear to be an outlier: Perez et al, (2017) Remission rate: Subgrouping by genetic test showed significant differences with NeuroIDgenetix and GeneSight between PGX-guided versus unguided treatment, but not with Neuropharmagen. CNSDose was not included in this analysis.	The current analysis provides preliminary support for improved response and remission rates in MDD when treatment is guided by pharmacogenomics
Rosenblat et al^Citation27	N/A	There was an 18.2% reduction in HAMD-17 in the unguided group vs 30.8% reduction in the guided group (p=0.04) in a non-randomized, prospective cohort study 77% of participants showed improvement, with 39% showing a treatment response and 38% achieving full remission as per QIDS-SR scores, regardless of number of previous antidepressants, in a 3-month naturalistic, Genecept Assay (Genomind, King of Prussia, Pennsylvania). At the end of the 12-week trial, subjects receiving CNSDose guided prescribing (n=74) had a 72% remission rate, while the unguided group (n=74) had a remission rate of 28% with a 2.52-fold greater chance of remission (95% CI: 1.71–3.73, p<0.0001) with NNT=3 (95% CI: 1.7–3.5) in a 12-week prospective RCT with Caucasian adults (N=148) with moderate to severe MDD	A limited number of studies have shown promise for the clinical utility of pharmacogenomic testing; Well-designed clinical trials with adequate sample sizes, randomization, and blinding are required
Brown et al^Citation28		Symptoms improvement: When either of the open-label trials were removed, there was no significant difference; Hall-Flavin et al, 2012 (Δ=9.54, 95% CI: −1.09–20.17, p=0.079) and Hall-Flavin et al, 2013 (Δ=5.76, 95% CI: −0.17–11.69, p=0.057) When the studies were grouped based on trial design, there was a statistically significant difference for the guided group for the RCTs and open-label studies, p<0.0045 and p<0.001, respectively Response: When each trial was removed, the analysis showed consistent results; significant response rate p<0.05 For analysis based on study type, guided group has shown statistical significance for both RCTs and open-label trials (RR=1.34, 95% CI: 1.10–1.62, p=0.004; and RR=1.72, 95% CI: 1.11–2.67, p=0.016), respectively Remission: When each trial was removed, the analysis showed no statistically significant difference except for Greden et al, p=0.075 When the studies were grouped based on trial design, there was no statistically significant difference between groups in the open-label trial, but there was significance in RCTs (RR=1.49, 95% CI: 1.14–1.96, p=0.004)	This study has shown improved outcomes (response, remission, and symptoms improvement) for patients with MDD and prior medication failure who received treatment guided by GeneSight test as compared to the unguided group. This was visible across all studies and when analysis was conducted for RCTs only
Randomized controlled trials
Han et al^Citation29	FIBSER: frequency (p=0.0346), intensity (p=0.0001), and burden (p=0.0001) at the end of 8 weeks between the two groups favoring PGX-guided treatment by 18.1%, 69.0%, and 69.7% of differences	Change in HAMD-17 score was significantly different between the two groups, favoring guided group by −4.1 points of difference (p=0.010) Response rate based on HAMD total score was also significantly higher in PGX-guided arm vs TAU at the end of treatment by 28.1% difference (p=0.014) Remission rate was numerically higher (19.9% difference) in PGX-guided arm than in TAU groups, without statistical difference (p=0.071) The mean changes from baseline to endpoint in PHQ-9 total scores in the PGX-guided and TAU groups were significantly different between the two groups, favoring PGX-guided arm by −3.8 points of difference (p=0.011) The mean changes from baseline to endpoint in PHQ-15 total scores in the PGX-guided and TAU groups were not significantly different between the two groups, but numerically favored PGX-guided arm by −1.7 points of difference (p=0.155)	The present study demonstrates that PGX testing may be a better option in the treatment of MDD in terms of effectiveness and tolerability; however, study shortcomings may limit a generalization. Adequately powered, well-designed studies are needed
Greden et al^Citation30	For the mean number of side effects at week 8, p=0.855 For the proportion of patients who experienced side effects, p=0.881	There was 30% improvement in response, and 50% improvement in remission among difficult-to-treat patients in the guided-care arm compared to TAU. Sustained improvement was observed at 24 weeks	These results from the GUIDED trial indicate that PGX testing is effective in improving response and remission rates among those with prior treatment resistance, particularly for patients who are treated with medications that are incongruent with their genetic profile
Thase et al^Citation31	N/A	Response rate (∆=8.0%, p=0.008) at week 8 favoring the guided arm Remission rate (∆=7.5%, p=0.003) at week 8 favoring the guided arm Durability of guided-care outcomes through week 24: 42.2% decrease in HDRS-17 scores at week 24 compared to baseline. This decrease in HDRS-17 score represents a 56% increase in symptom improvement from week 8 At week 24, the response rate was 44.3% and the remission rate was 33.2% Outcomes in patients who switched medications: HAMD-17 scores decreased by 30.0% from baseline to week 8 in the guided-care arm compared to 22.3% in TAU (∆=7.6%, p=0.011) The response rate at week 8 among patients who switched medications was 29.8% in the guided-care arm compared to 19.4% for TAU (∆=10.4%, p=0.011) The remission rate at week 8 for patients who switched medications in the guided-care arm was 20.3% compared to 11.1% in TAU (∆=9.2%, p=0.008) This represents a relative improvement of 54% for response and 83% for remission among patients whose medication switches were informed by pharmacogenomic testing	All patient outcomes remained significantly improved for the guided-care arm vs TAU when the subset of patients who switched medications were evaluated separately. Patients with treatment-resistant depression have a low likelihood of reaching remission with standard treatment approaches

Abbreviations: PGX, pharmacogenetic; TAU, treatment as usual; MDD, major depressive disorder; DSM-5, Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition; HAMD-17, 17-item Hamilton Depression Rating Scale; PHQ-9, Patient Health Questionnaire-9; QIDS-C16, Clinician-rated Quick Inventory of Depressive Symptomatology; QIDS-SR16, Self-Rated Quick Inventory of Depressive Symptomatology; FIBSER, Frequency, Intensity, and Burden of Side Effects Rating; RCT, randomized controlled trial; RR, risk ratio; NNT, number needed to treat.

Table 5 CCAT Quality Scores of Eligible Systematic Reviews

Study	Domain Score								Overall Score
	Preliminaries	Introduction	Design	Sampling	Data Collection	Ethical Matters	Results	Discussion
Brown et al^Citation28	3	4	1	2	0	4	4	3	51%
Rosenblat et al^Citation27	3	5	2	2	0	2	3	3	53%
Health Quality Ontario ^Citation24	4	5	3	5	0	1	3	1	55%
Fabbri et al^Citation25	2	5	2	4	1	5	2	3	60%
Rosenblat et al^Citation26	5	5	4	3	5	4	3	4	83%
Bousman et al^Citation23	5	5	3	4	5	5	5	3	88%

Notes: Poor quality (0–50%), moderate quality (51–74%), high quality (75–100%).

Table 6 CCAT Quality Scores of Eligible Randomized Controlled Trials (RCTs)

Study	Domain Score								Overall Score
	Preliminaries	Introduction	Design	Sampling	Data Collection	Ethical Matters	Results	Discussion
Han et al^Citation29	3	4	3	2	1	3	3	5	59%
Thase et al^Citation31	5	5	4	1	4	4	4	3	75%
Greden et al^Citation30	4	4	5	2	5	4	4	5	84%

Notes: Poor quality (0–50%), moderate quality (51–74%), high quality (75–100%).

DNA Medical Testing. Genetic Testing | geneSight. GeneSight. 2020. Available from: https://genesight.com/. Accessed 1021, 2020.

 Google Scholar

Dynacare - GENECEPT ASSAY (English - Canada). Dynacare.ca. 2020. Available from: https://www.dynacare.ca/specialpages/secondarynav/find-a-test/nat/genecept%C2%A0assay.aspx?sr=ont&st=&. Accessed 1021, 2020.

 Google Scholar

CNSdose | Genetic Testing | Home. Cnsdose.com. 2021. Available from: https://cnsdose.com/. Accessed 1021, 2020.

 Google Scholar

Precision medicine especially developed for psychiatry | AB-Biotics. AB-Biotics. 2021. Available from: https://www.ab-biotics.com/c/precision-medicine/. Accessed 321, 2021.

 Google Scholar

Jain K Applications of AmpliChip™ CYP450. 2020.

 Google Scholar

AltheaDx. Depression and Anxiety. 2020. Available from: https://www.altheadx.com/clinical-trial-portfolio/idgenetix-tests/. Accessed 1021, 2020.

 Google Scholar

Genelex . Precision Medicine Made Possible with Pharmacogenetics. Genelex.com. 2020. Available from: https://www.genelex.com/. Accessed 1021, 2020.

 Google Scholar

Genomas:: Rennova Health, Inc. (RNVA). Rennovahealth.com. 2021. Available from: https://www.rennovahealth.com/brands/genomas. Accessed 1021, 2020.

 Google Scholar

Pillcheck. Tailor your medications with Pillcheck DNA analysis. Pillcheck. 2020. Available from: https://www.pillcheck.ca/. Accessed 1021, 2020.

 Google Scholar

Health Quality OntarioH. Pharmacogenomic Testing for Psychotropic Medication Selection: a Systematic Review of the Assurex GeneSight Psychotropic Test. PubMed Central (PMC). 2021. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5433545/. Accessed, 2019.

 Google Scholar

Bousman C, Arandjelovic K, Mancuso S, Eyre H, Dunlop B. Pharmacogenetic tests and depressive symptom remission: a meta-analysis of randomized controlled trials. Pharmacogenomics. 2019;20(1):37–47.30520364

 PubMed Web of Science ®Google Scholar

Fabbri C, Zohar J, Serretti A. Pharmacogenetic tests to guide drug treatment in depression: comparison of the available testing kits and clinical trials. Prog Neuropsychopharmacol Biol Psychiatry. 2018;86:36–44.29777729

 PubMed Web of Science ®Google Scholar

Rosenblat J, Lee Y, McIntyre R. The effect of pharmacogenomic testing on response and remission rates in the acute treatment of major depressive disorder: a meta-analysis. J Affect Disord. 2018;241:484–491.30149336

 PubMed Web of Science ®Google Scholar

Rosenblat J, Lee Y, McIntyre R. Does pharmacogenomic testing improve clinical outcomes for major depressive disorder? J Clin Psychiatry. 2017;78(06):720–729.28068459

 PubMed Web of Science ®Google Scholar

Brown L, Vranjkovic O, Li J, et al. The clinical utility of combinatorial pharmacogenomic testing for patients with depression: a meta-analysis. Pharmacogenomics. 2020;21(8):559–569.32301649

 PubMed Web of Science ®Google Scholar

Han C, Wang S, Bahk W, et al. A pharmacogenomic-based antidepressant treatment for patients with major depressive disorder: results from an 8-week, randomized, single-blinded clinical trial. Clin Psychopharmacol Neurosci. 2018;16(4):469–480.30466219

 PubMed Web of Science ®Google Scholar

Greden J, Parikh S, Rothschild A, et al. Impact of pharmacogenomics on clinical outcomes in major depressive disorder in the GUIDED trial: a large, patient- and rater-blinded, randomized, controlled study. J Psychiatr Res. 2019;111:59–67.30677646

 PubMed Web of Science ®Google Scholar

Thase M, Parikh S, Rothschild A, et al. Impact of pharmacogenomics on clinical outcomes for patients taking medications with gene-drug interactions in a randomized controlled trial. J Clin Psychiatry. 2019;80:6.

 Web of Science ®Google Scholar