Efficacy of prospective pharmacogenetic testing in the treatment of major depressive disorder: Results of a randomized, double-blind clinical trial

Background: A 12-week, double-blind, parallel, multi-center randomized controlled trial in 316 adult patients with major depressive disorder (MDD) was conducted to evaluate the effectiveness of pharmacogenetic (PGx) testing for drug therapy guidance. Methods: Patients with a CGI-S = 4 and requiring...

Descripción completa

Detalles Bibliográficos
Autores: Pérez V., Salavert A., Espadaler J., Tuson M., Saiz-Ruiz J., Sáez-Navarro C., Bobes J., Baca-García E., Vieta E., Olivares J.M., Rodriguez-Jimenez R., Villagrán J.M., Gascón J., Cañete-Crespillo J., Solé M., Saiz P.A., Ibáñez, de Diego-Adeliño J., Menchón J.M., álvarez E., Garriga M., Castaño J., Díez-Aja C., Sánchez-González R., Bagney A., García-Portilla M.P., Bauzà J., Bernardo M., Rodao J.M., Mercè Brat, Mongil J.M., Garrido J.M., Holgado P.M., Aguilar E., Safont G., Martín-del Moral M., Quintero J., Mora F., Barrigón M.L., Villoria L., Soria V., Blanch J., Rissech N., Puigmulé M., Bonachera M.À., Mayoral-Cleries F., Cantero N., Palao D.J., Irastorza L.J., Navarro R.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2017
País:España
Institución:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
Repositorio:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
OAI Identifier:oai:iibsantpau.fundanetsuite.com:p10394
Acceso en línea:https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=10394
https://ddd.uab.cat/record/253924
Access Level:acceso abierto
Palabra clave:antidepressant agent
adult
Article
Clinical Global Impression scale
computer analysis
controlled study
double blind procedure
drug indication
drug safety
drug tolerability
female
follow up
genetic screening
human
major clinical study
major depression
male
multicenter study
parallel design
pharmacogenetics
psychiatrist
randomized controlled trial
treatment duration
treatment response
clinical trial
genetics
middle aged
pharmacogenetic testing
treatment outcome
Adult
Antidepressive Agents
Depressive Disorder, Major
Double-Blind Method
Female
Humans
Male
Middle Aged
Pharmacogenomic Testing
Treatment Outcome
Descripción
Sumario:Background: A 12-week, double-blind, parallel, multi-center randomized controlled trial in 316 adult patients with major depressive disorder (MDD) was conducted to evaluate the effectiveness of pharmacogenetic (PGx) testing for drug therapy guidance. Methods: Patients with a CGI-S = 4 and requiring antidepressant medication de novo or changes in their medication regime were recruited at 18 Spanish public hospitals, genotyped with a commercial PGx panel (Neuropharmagen®), and randomized to PGx-guided treatment (n = 155) or treatment as usual (TAU, control group, n = 161), using a computer-generated random list that locked or unlocked psychiatrist access to the results of the PGx panel depending on group allocation. The primary endpoint was the proportion of patients achieving a sustained response (Patient Global Impression of Improvement, PGI-I = 2) within the 12-week follow-up. Patients and interviewers collecting the PGI-I ratings were blinded to group allocation. Between-group differences were evaluated using ?2-test or t-test, as per data type. Results: Two hundred eighty patients were available for analysis at the end of the 12-week follow-up (PGx n = 136, TAU n = 144). A difference in sustained response within the study period (primary outcome) was not observed (38.5% vs 34.4%, p = 0.4735; OR = 1.19 [95%CI 0.74-1.92]), but the PGx-guided treatment group had a higher responder rate compared to TAU at 12 weeks (47.8% vs 36.1%, p = 0.0476; OR = 1.62 [95%CI 1.00-2.61]), and this difference increased after removing subjects in the PGx-guided group when clinicians explicitly reported not to follow the test recommendations (51.3% vs 36.1%, p = 0.0135; OR = 1.86 [95%CI 1.13-3.05]). Effects were more consistent in patients with 1-3 failed drug trials. In subjects reporting side effects burden at baseline, odds of achieving a better tolerability (Frequency, Intensity and Burden of Side Effects Rating Burden subscore =2) were higher in the PGx-guided group than in controls at 6 weeks and maintained at 12 weeks (68.5% vs 51.4%, p = 0.0260; OR = 2.06 [95%CI 1.09-3.89]). Conclusions: PGx-guided treatment resulted in significant improvement of MDD patient's response at 12 weeks, dependent on the number of previously failed medication trials, but not on sustained response during the study period. Burden of side effects was also significantly reduced. © 2017 The Author(s).

Similares en LA Referencia