Meta-analysis of the data on differences in the exposure to psychiatric drugs between poor and normal cYP2C19/CYP2D6 metabolizers
Bibliographic record
Abstract
Postoji mogućnost da genetski predodređene razlike između osoba u kapacitetu CYP450enzima mogu uticati na farmakoterapiju u psihijatriji. Cilj ovog istraživanja bio je preciznakvantifikacije uticaja CYP2C19/CYP2D6 fenotipa na izloženost antidepresivima iantipsihoticima metodom meta-analize odnosa srednjih vrednosti. Drugi cilj bio jeispitivanje uticaja CYP2C19 fenotipa na efikasnost i podnošljivost antidepresiva pomoćukliničke studije u kojoj su hospitalizovani pacijenti praćeni četiri nedelje.Serija meta-analiza podataka iz 94 jedinstvene studije na ukupno 8379 precizno jekvantifikovala povećanu izloženost escitalopramu (+163%; 95%CI: +140%, 189%;n=1262, p<0,0001) i sertralinu (+38%; 95%CI: +27%, +51%; n=917, p<0,0001) kod osobasa genetski predviđenim smanjenim kapacitetom CYP2C19 enzima, kao i povećanuizloženost risperidonu (+36%; 95%CI: +28%, +44%; n=1492, p<0,0001), aripiprazolu(+48%; 95%CI: +41%, +57%; n=1038, p<0,0001) i haloperidolu (+68%; CI95%: 40%,102%; n=423, p<0.0001) kod osoba sa genetski predviđenim smanjenim kapacitetomCYP2D6 enzima. Klinička studija demonstrirala je da su, u toku četiri nedelje, osobe sasporijim CYP2C19 metabolizmom imale 36% (95%CI: 20-52%, p<0,0001) manje izraženopoboljšanje simptoma depresije (praćeno Hamilton skalom za depresiju) i značajno većiintenzitet neželjenih efekata vezanih za gastrointestinalni (q=0,002) i centralni nervnisistem (q=0,045) što je mereno Toronto skalom, u odnosu na kontrolne osobe.Zbog visoke preciznosti kvantifikacije, rezultati meta-analiza mogu poslužiti kao osnova zakliničke smernice za precizno doziranje ispitivanih lekova na osnovu CYP2C19/CYP2D6genotipa. Takođe, rezultati kliničke studije naglašavaju da CYP2C19 genotip može bitiklinički važna informacija u psihijatrijskoj praksi.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot 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.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.005 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.001 | 0.004 |
| Science and technology studies | 0.002 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.005 | 0.003 |
| Research integrity | 0.000 | 0.003 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
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".