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

Víctor Pérez, Ariana Salavert, Jordi Espadaler, Miquel Tuson, Jerónimo Saiz-Ruiz, Cristina Sáez-Navarro, Julio Bobes, Enrique Baca-García, Eduard Vieta, José M. Olivares, Roberto Rodriguez-Jimenez, José M. Villagrán, Josep Gascón, Josep Cañete-Crespillo, Montse Solé, Pilar A. Saiz, Ángela Ibáñez, Javier de Diego-Adeliño, José M. Menchón, Enric álvarezMarina Garriga, Juan Castaño, Cristobal Díez-Aja, Roberto Sánchez-González, Alexandra Bagney, María Paz García-Portilla, Joana Bauzà, Miquel Bernardo, José M. Rodao, Mercè Brat, José M. Mongil, Juan Miguel Garrido, Pedro M. Holgado, Eva Aguilar, Gemma Safont, Mercedes Martín-del Moral, Javier Quintero, Fernando Mora, María Luisa Barrigón, Lucía Villoria, Virginia Soria, Jordi Blanch, Núria Rissech, Marta Puigmulé, Miquel Àngel Bonachera, Fermín Mayoral-Cleries, Nazaret Cantero, Diego J. Palao, Luis Javier Irastorza, Rafael Navarro

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Abstract

© 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.
Original languageEnglish
Article number250
JournalBMC Psychiatry
Volume17
Issue number1
DOIs
Publication statusPublished - 14 Jul 2017

Keywords

  • Antidepressant response
  • Depression
  • Pharmacogenetics
  • Precision medicine
  • Randomized clinical trial

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