RT Journal Article
T1 Efficacy of prospective pharmacogenetic testing in the treatment of major depressive disorder: results of a randomized, double-blind clinical trial.
A1 Pérez, Víctor
A1 Salavert, Ariana
A1 Espadaler, Jordi
A1 Tuson, Miquel
A1 Saiz-Ruiz, Jerónimo
A1 Sáez-Navarro, Cristina
A1 Bobes, Julio
A1 Baca-García, Enrique
A1 Vieta, Eduard
A1 Olivares, José M
A1 Rodriguez-Jimenez, Roberto
A1 Villagrán, José M
A1 Gascón, Josep
A1 Cañete-Crespillo, Josep
A1 Solé, Montse
A1 Saiz, Pilar A
A1 Ibáñez, Ángela
A1 de Diego-Adeliño, Javier
A1 AB-GEN Collaborative Group, 
A1 Menchón, José M
K1 Antidepressant response
K1 Depression
K1 Pharmacogenetics
K1 Precision medicine
K1 Randomized clinical trial
AB 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. 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 χ2-test or t-test, as per data type. 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]). 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. European Clinical Trials Database 2013-002228-18 , registration date September 16, 2013; ClinicalTrials.gov NCT02529462 , retrospectively registered: August 19, 2015.
YR 2017
FD 2017-07-14
LK http://hdl.handle.net/10668/11405
UL http://hdl.handle.net/10668/11405
LA en
DS RISalud
RD Apr 7, 2025