Efficacy of prospective pharmacogenetic testing in the treatment of major depressive disorder : results of a randomized, double-blind clinical trial
Pérez Solà, Víctor (Institut Hospital del Mar d'Investigacions Mèdiques)
Salavert, Ariana (AB-Biotics S.A)
Espadaler Mazo, Jordi (AB-Biotics S.A)
Tuson, Miquel (AB-Biotics S.A)
Saiz-Ruiz, Jerónimo (Instituto Ramón y Cajal de Investigación Sanitaria (Madrid))
Sáez-Navarro, Cristina (Hospital Universitari Joan XXIII de Tarragona)
Bobes, Julio (Universidad de Oviedo)
Baca-García, Enrique (Columbia University)
Vieta, Eduard (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Olivares, José M.. (Complexo Hospitalario Universitario de Vigo)
Rodriguez-Jimenez, Roberto (Instituto de Investigación Sanitaria Hospital 12 de Octubre (i+12))
Villagrán, José M. (Hospital Universitario de Jerez (Jerez de la Frontera))
Gascón Barrachina, Josep (Mútua de Terrassa)
Cañete-Crespillo, Josep (Hospital de Mataró. Consorci Sanitari del Maresme)
Solé, Montse (Hospital Universitari Joan XXIII de Tarragona)
Saiz, Pilar A. (Universidad de Oviedo)
Ibáñez, Ángela (Instituto Ramón y Cajal de Investigación Sanitaria (Madrid))
de Diego-Adeliño, Javier (Institut d'Investigació Biomèdica Sant Pau)
Menchón, José M. (Universitat de Barcelona)
Universitat Autònoma de Barcelona

Data:	2017
Resum:	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 , registration date September 16, 2013; , retrospectively registered: August 19, 2015. The online version of this article (doi:10. 1186/s12888-017-1412-1) contains supplementary material, which is available to authorized users.
Ajuts:	Ministerio de Economía, Industria y Competitividad PTQ-11-05076 Ministerio de Economía, Industria y Competitividad PTQ11-04914 Ministerio de Economía, Industria y Competitividad INC-FPGS-2011-2223 Ministerio de Economía, Industria y Competitividad INC-FPGS-2011-2224
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Depression ; Pharmacogenetics ; Precision medicine ; Antidepressant response ; Randomized clinical trial
Publicat a:	BMC Psychiatry, Vol. 17 (july 2017) , ISSN 1471-244X

DOI: 10.1186/s12888-017-1412-1
PMID: 28705252

13 p, 734.0 KB

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