Table 2:

Summary of Study Design and Characteristics of Included Studies

Author, Year Country	Study Design	N PGx/TAU	Setting and Provider Type	Inclusion Criteria	Exclusion Criteria	PGx Test, No. Genes	Length of FU, wk
GeneSight Studies
GUIDED trial, Greden et al, 201957 United States Post hoc Analyses Thase et al, 201968; Dunlop et al, 201966; Forester et al, 202067	RCT	760/781	• Outpatients from 60 academic and community sites • Psychiatric and primary care providers	• Age ≥ 18 • MDD (≥ 11 QIDS-C16 and QIDS-SR16 rating scale) • Inadequate response (no clinical improvement or intolerable SEs) to at least one treatment included in test report within current episode Forester et al, 2020, Subgroup • Aged 65 years or older Thase et al, 2019, Subgroup • Taking medications subject to gene-drug interactions at baselinea	• Significant suicide risk • Severe co-occurring psychiatric or cognitive disordersb • Unstable or significant medical conditionsb • Inpatients Per Protocol Cohort • HAM-D17 < 14 at baseline • Protocol violations or clinician did not view test report	GeneSight, 8 genes	8
Winner et al, 201365 United States	RCT	26/25	• Outpatient clinics • Psychiatrists, psychiatric NPs	• MDD or depressive disorder NOS • HAM-D17 ≥ 14	• Bipolar disorder, schizophrenia, schizoaffective disorders, active substance abuse or dependence • ECT • Depression requiring hospitalization	GeneSight, 5 genes	10
Hall-Flavin et al, 201355 United States	Prospective cohort	114/113	• Outpatient hospital clinic • Psychiatrists	• Aged 18–72 y • Primary diagnosis of MDD or depressive disorder NOS (DSM-IV) • HAM-D17 ≥ 14	Bipolar disorder type I, schizophrenia, or schizoaffective disorder	GeneSight, 5 genes	8
Hall-Flavin et al, 201256 United States	Prospective cohort	25/26	• Outpatient behavioural clinic • Psychiatrist	• Aged 25–75 • Primary diagnosis of MDD based on DSM-IV (HAM-D17 ≥ 14)	Bipolar disorder type I, schizophrenia, or schizoaffective disorder	GeneSight, 5 genes	8
Neuropharmagen Studies
Han et al, 201860 Korea	RCT	52/48	• 2 university teaching hospitals • Psychiatrists	• Aged ≥ 20 y • MDD (DSM-5) • ≥ 3 on CGI-I despite current treatment with proper dose and duration (≥ 6 wk) OR intolerance to current therapy	• Not receiving antidepressant • Other psychiatric diagnosesb • Hospitalized within 8 wk• CBT or other psychotherapy • Clinical trial in past month • ECT within 8 wk • Pregnant or breastfeeding	Neuro-pharmagen, 20 genes	8
Perez et al, 201762 Spain Post hoc Subgroups Menchon et al, 201969	RCT	155/161	• Outpatients and inpatients from 18 hospitals and mental health centres • Psychiatrists	• Aged ≥ 18 y • MDD (DSM-5) • CGI-S ≥ 4 at screening and randomization • Required medication de novo or receiving treatment and required substitution or augmentation with antidepressant	• Primary psychiatric diagnoses other than MDD • Pregnant or breastfeeding • Treatment with quinidine, cinacalcet, or terbinafine Per Protocol Analysis • Clinician prescribed against test recommendation	Neuro-pharmagen, 30 genes	12
Other Pharmacogenomic Tests
Perlis et al, 202061 United States	RCT	151/153	• 21 outpatient centres • Not specified	• Aged 18–75 y • Primary diagnosis of nonpsychotic MDD (DSM-5, MINI 7.0) • SIGH-D17 score > 18 • Failure (inefficacy or intolerable AEs) of at least one prior adequate trial of standard antidepressant for current episode	• Other psychiatric diagnosesb • History of suicidal behaviour within 12 mo or active suicidal thoughts with intent • 4 or more failed pharmacologic interventions in current episode • ECT, TMS, or psychotherapy (CBT or DBT) within 90 d • Current psychotherapy allowed if frequency is not increased • Unstable or active medical conditions (that could jeopardize safety or participation)c	Genecept, 18 genes	8
Bradley et al, 201858 United States	RCT	352/333 randomized (depresssion cohort: 237/213)	• 20 independent clinical sites in psychiatry, obstetrics and gynecology, internal medicine, family medicine	• Aged 19–87 y • Depression or anxiety (DSM-5 or site procedures and MINI Psychiatric interview)d • New to treatment (newly diagnosed or treated for < 6 wk) or inadequately controlled (lack of efficacy or discontinuation due to AE or intolerability)	• Bipolar disorder, schizophrenia, personality disorder, traumatic physical injury • Significant risk for suicide or hospitalization • History of chronic renal dysfunction or chronic kidney disease, malabsorption, pregnancy, abnormal hepatic function	NeuroID-genetix, 10 genes	12
Shan et al, 201963 China	RCT	31/43	• Single-hospital outpatients and inpatients • Same psychiatrist treated both groups	• Aged 18–51 y • MDD (DSM-5) • HAM-D17 ≥ 17, and depressive mood ≥ 2 • No psychotic symptoms • At least a junior high school education level • Han population in China • Treatment naive or interrupted medication for > 2 wk (4 wk for fluoxetine)	• Any other diagnosis on DSM-5 • Physical illness (e.g., liver and kidney disease, CV diseases) • Any combination with other antipsychotic medications, including typical and atypical antipsychotic and mood stabilizer • Pregnancy	Not specified, 5 genes	8
Singh et al, 201564 Australia	RCT	74/74	• NR • Psychiatrist	• Principal diagnosis of MDD (DSM-5) • HAM-D > 18 • Caucasian only	• Other active psychiatric diagnosesb • Pregnant or breastfeeding • Hepatic or renal impairment • Co-prescribed CYP2D6, CYP2C19, ABCB1 inducers or inhibitors • Grapefruit juice drinker or smokers	CNSDose, NR	12

Abbreviations: AABCB1, ATP binding cassette subfamily B member 1; AE, adverse effect; C16, clinician rated; CBT, cognitive behavioural therapy; CGI, Clinical Global Impressions Scale I (improvement) or S (severity of illness); CV, cardiovascular; CYP, cytochrome P; DBT, dialectical behaviour therapy; DSM, Diagnostic and Statistical Manual of Mental Disorders; ECT, electroconvulsive therapy; FU, follow-up; HAM-D, Hamilton Depression Rating Scale; MDD, major depressive disorder; MINI 7.0, Mini International Neuropsychiatric Interview, Version 7.0; SIGH-D17, 17-item version of the Structured Interview Guide for the Hamilton Depression Rating Scale; NOS, not otherwise specified; NP, nurse practitioner; NR, not reported; PGx, pharmacogenomic testing group; QIDS, Quick Inventory of Depressive Symptomatology; RCT, randomized controlled trial; SE, side effect; TAU, treatment as usual; TMS, transcranial magnetic stimulation.

^aPatients in the “use with caution” and “use with increased caution and with more frequent monitoring” categories.

^bFull list of excluded conditions listed in supplementary methods for primary article.

^cIn the opinion of the site investigator; list of examples provided in primary article.

^dOnly data for the depression cohort were used in the present analysis (excluding those with anxiety alone).