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Record W4296034623 · doi:10.1002/cpt.2748

Pharmacogenomic Testing and Depressive Symptom Remission: A Systematic Review and <scp>Meta‐Analysis</scp> of Prospective, Controlled Clinical Trials

2022· review· en· W4296034623 on OpenAlexaff
Lisa Brown, Joseph D. Stanton, Kanika Bharthi, Abdullah Al Maruf, Daniel J. Müller, Chad Bousman

Bibliographic record

VenueClinical Pharmacology & Therapeutics · 2022
Typereview
Languageen
FieldPharmacology, Toxicology and Pharmaceutics
TopicPharmacogenetics and Drug Metabolism
Canadian institutionsUniversity of TorontoAlberta Children's HospitalCentre for Addiction and Mental HealthUniversity of ManitobaChildren's Hospital Research Institute of ManitobaUniversity of Calgary
Fundersnot available
KeywordsMeta-analysisPharmacogenomicsClinical trialMedicineMEDLINEInternal medicinePharmacology

Abstract

fetched live from OpenAlex

Pharmacogenomic (PGx) testing has emerged as a compelling strategy that clinicians can use to inform antidepressant medication selection and dosing, but the clinical efficacy of this strategy has been questioned. We systematically reviewed and meta-analyzed clinical trials for an association between the use of PGx-guided antidepressant therapy and depressive symptom remission in patients with major depressive disorder (MDD). We included prospective, controlled clinical trials published in English up to July 12, 2022. Data extraction and synthesis adhered to the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Each trial was assessed for risk of bias and a random-effects model was used to estimate pooled risk ratios. Thirteen trials comprising 4,767 patients were analyzed, including 10 randomized controlled trials, and three open label trials. Across all included trials, those that received PGx-guided antidepressant therapy (n = 2,395) were 1.41 (95% confidence interval (CI) = 1.15-1.74, P = 0.001) more likely to achieve remission compared with those that received unguided antidepressant therapy (n = 2,372). Pooled risk ratios for randomized controlled trials and open label trials were 1.46 (95% CI: 1.13-1.88) and 1.26 (95% CI = 0.84-1.88), respectively. These results suggest that PGx-guided antidepressant therapy is associated with a modest but significant increase in depressive symptom remission in adults with MDD. Efforts to address the heterogeneity in PGx test composition (i.e., genes and alleles tested) and accompanying prescribing recommendations across trials will likely reduce the uncertainty about the efficacy of PGx-guided antidepressant therapy in the literature.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.044
metaresearch head score (Gemma)0.007
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMetaresearch, Meta-epidemiology (narrow), Meta-epidemiology (broad), Research integrity, Insufficient payload (model declined to judge)
Consensus categoriesMeta-epidemiology (narrow), Research integrity
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Meta-analysis · Consensus signal: Meta-analysis
GenreCandidate signal: Review · Consensus signal: Review
Teacher disagreement score0.354
Threshold uncertainty score0.999

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0440.007
Meta-epidemiology (narrow)0.0020.001
Meta-epidemiology (broad)0.0350.009
Bibliometrics0.0010.002
Science and technology studies0.0010.002
Scholarly communication0.0000.000
Open science0.0020.001
Research integrity0.0020.007
Insufficient payload (model declined to judge)0.0020.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.645
GPT teacher head0.616
Teacher spread0.029 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; both teacher heads agree on what is shown here.

Study designMeta-analysis
Domainnot available
GenreReview

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations115
Published2022
Admission routes1
Has abstractyes

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