Impact of pharmacogenomics on clinical outcomes in major depressive disorder in the GUIDED trial: A large, patient- and rater-blinded, randomized, controlled study

Greden, John F.; Parikh, Sagar V.; Rothschild, Anthony J.; Thase, Michael E.; Dunlop, Boadie W.; DeBattista, Charles; Conway, Charles R.; Forester, Brent P.; Fm, Mondimore; Shelton, Richard C.; Macaluso, Matthew; Li, James; Brown, Krystal; Gilbert, Alexa; Burns, Lindsey; Jablonski, Michael; Dechairo, Bryan

doi:10.1016/j.jpsychires.2019.01.003

Cited by 221 publications

(232 citation statements)

References 27 publications

Supporting

Mentioning

222

Contrasting

Unclassified

Order By: Relevance

“…The RCTs published to date presented encouraging results but they were not free from potential sources of bias. [69][70][71][72][73][74][75] Of note, some were not double-blind, had power issues and were heterogeneous in their design and methods. These RCTs investigated five different pharmacogenetic tests, each with specific characteristics in terms of included variants and algorithm used to predict treatment outcomes.…”

Section: Clinical Applicationsmentioning

confidence: 99%

Pharmacogenetics and Depression: A Critical Perspective

Corponi

Fabbri

Serretti

2019

Psychiatry Investig

View full text Add to dashboard Cite

Depression leads the higher personal and socio-economical burden within psychiatric disorders. Despite the fact that over 40 antidepressants (ADs) are available, suboptimal response still poses a major challenge and is thought to be partially a result of genetic variation. Pharmacogenetics studies the effects of genetic variants on treatment outcomes with the aim of providing tailored treatments, thereby maximizing efficacy and tolerability. After two decades of pharmacogenetic research, variants in genes coding for the cytochromes involved in ADs metabolism (CYP2D6 and CYP2C19) are now considered biomarkers with sufficient scientific support for clinical application, despite the lack of conclusive cost/effectiveness evidence. The effect of variants in genes modulating ADs mechanisms of action (pharmacodynamics) is still controversial, because of the much higher complexity of ADs pharmacodynamics compared to ADs metabolism. Considerable progress has been made since the era of candidate gene studies: the genomic revolution has made possible to assess genetic variance on an unprecedented scale, throughout the whole genome, and to analyze the cumulative effect of different variants. The results have revealed key information on the biological mechanisms mediating ADs effect and identified hypothetical new pharmacological targets. They also paved the way for future availability of polygenic pharmacogenetic panels to predict treatment outcome, which are expected to explain much higher variance in ADs response compared to CYP2D6 and CYP2C19 only. As the demand and availability of AD pharmacogenetic testing is projected to increase, it is important for clinicians to keep abreast of this evolving area to facilitate informed discussions with their patients. Psychiatry Investig 2019;16(9):645-653cc This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/bync/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

show abstract

Section: Clinical Applicationsmentioning

confidence: 99%

Pharmacogenetics and Depression: A Critical Perspective

Corponi

Fabbri

Serretti

2019

Psychiatry Investig

View full text Add to dashboard Cite

show abstract

“…2 While using symptom improvement as the outcome variable showed no significance (P = 0.107), patients guided by the test achieved a significant improvement in response (≥50% decrease in 17-item Hamilton Rating Scale for Depression [HAMD-17]; P = 0.013) and remission (HAMD-17 ≤ 7; P = 0.007), compared with those who received TAU. Notably, a recent meta-analysis of multigene PGx tests (incorporating the study by Greden et al 2 and four other RCTs) reported that the PGx test-guided groups (n = 887) showed significantly better remission rates (odds ratio of 1.7) compared to the non-guided (TAU) group (n = 850). 3 Given that a high proportion of patients with depression is treated by primary care providers, the utility of PGx testing was evaluated in primary (N = 810) and psychiatric (N = 1061) care settings in a subset of the IMPACT project (a 7-year naturalistic study examining the effects of PGx testing).…”

mentioning

confidence: 95%

“…Some companies have conducted prospective evaluation trials examining the benefits of genetic testing versus treatment as usual (TAU). The largest trial to date was recently completed and consisted of an 8‐week double‐blind, multicenter, randomized controlled trial (RCT) of the Genesight commercial test versus TAU in depression ( N = 1167) . While using symptom improvement as the outcome variable showed no significance ( P = 0.107), patients guided by the test achieved a significant improvement in response (≥50% decrease in 17‐item Hamilton Rating Scale for Depression [HAMD‐17]; P = 0.013) and remission (HAMD‐17 ≤ 7; P = 0.007), compared with those who received TAU.…”

mentioning

confidence: 99%

“…While using symptom improvement as the outcome variable showed no significance ( P = 0.107), patients guided by the test achieved a significant improvement in response (≥50% decrease in 17‐item Hamilton Rating Scale for Depression [HAMD‐17]; P = 0.013) and remission (HAMD‐17 ≤ 7; P = 0.007), compared with those who received TAU. Notably, a recent meta‐analysis of multigene PGx tests (incorporating the study by Greden et al . and four other RCTs) reported that the PGx test‐guided groups ( n = 887) showed significantly better remission rates (odds ratio of 1.7) compared to the non‐guided (TAU) group ( n = 850) …”

mentioning

confidence: 99%

See 1 more Smart Citation

The coming‐of‐age of pharmacogenetic testing in clinical psychiatry

Yoshida

Müller

Kennedy

2019

Psychiatry Clin Neurosci

View full text Add to dashboard Cite

“…Fortunately, several more robust studies have been recently completed or are underway. 4,5 An additional benefit of pharmacogenetic tests is that they assess for germline mutations that do not change over a patient's lifetime; therefore, the data generated by a pharmacogenetic test could be used to guide future medication choices for the same patient. This may increase the value of the data generated by these tests over time.…”

mentioning

confidence: 99%