TY - JOUR
T1 - Efficacy of prospective pharmacogenetic testing in the treatment of major depressive disorder: Results of a randomized, double-blind clinical trial
AU - Pérez, Víctor
AU - Salavert, Ariana
AU - Espadaler, Jordi
AU - Tuson, Miquel
AU - Saiz-Ruiz, Jerónimo
AU - Sáez-Navarro, Cristina
AU - Bobes, Julio
AU - Baca-García, Enrique
AU - Vieta, Eduard
AU - Olivares, José M.
AU - Rodriguez-Jimenez, Roberto
AU - Villagrán, José M.
AU - Gascón, Josep
AU - Cañete-Crespillo, Josep
AU - Solé, Montse
AU - Saiz, Pilar A.
AU - Ibáñez, Ángela
AU - de Diego-Adeliño, Javier
AU - Menchón, José M.
AU - álvarez, Enric
AU - Garriga, Marina
AU - Castaño, Juan
AU - Díez-Aja, Cristobal
AU - Sánchez-González, Roberto
AU - Bagney, Alexandra
AU - García-Portilla, María Paz
AU - Bauzà, Joana
AU - Bernardo, Miquel
AU - Rodao, José M.
AU - Mercè Brat, empty
AU - Mongil, José M.
AU - Garrido, Juan Miguel
AU - Holgado, Pedro M.
AU - Aguilar, Eva
AU - Safont, Gemma
AU - Martín-del Moral, Mercedes
AU - Quintero, Javier
AU - Mora, Fernando
AU - Barrigón, María Luisa
AU - Villoria, Lucía
AU - Soria, Virginia
AU - Blanch, Jordi
AU - Rissech, Núria
AU - Puigmulé, Marta
AU - Bonachera, Miquel Àngel
AU - Mayoral-Cleries, Fermín
AU - Cantero, Nazaret
AU - Palao, Diego J.
AU - Irastorza, Luis Javier
AU - Navarro, Rafael
PY - 2017/7/14
Y1 - 2017/7/14
N2 - © 2017 The Author(s). 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 χ2-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.
AB - © 2017 The Author(s). 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 χ2-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.
KW - Antidepressant response
KW - Depression
KW - Pharmacogenetics
KW - Precision medicine
KW - Randomized clinical trial
U2 - https://doi.org/10.1186/s12888-017-1412-1
DO - https://doi.org/10.1186/s12888-017-1412-1
M3 - Article
VL - 17
JO - BMC Psychiatry
JF - BMC Psychiatry
SN - 1471-244X
IS - 1
M1 - 250
ER -