Table 3.

Characteristics of Eligible Randomized Controlled Trials (RCTs)

Study	Aim	Study Design	Sample Size	Eligibility Criteria	Population
Han et al29	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 al30	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 al31	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,30 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 al30

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.