Efficacy of prospective pharmacogenetic testing in the treatment of major depressive disorder: results of a randomized, double-blind clinical trial
Abstract 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 req...
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2017-07-01
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Online Access: | http://link.springer.com/article/10.1186/s12888-017-1412-1 |
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Article |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
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 AB-GEN Collaborative Group José M. Menchón |
spellingShingle |
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 AB-GEN Collaborative Group José M. Menchón Efficacy of prospective pharmacogenetic testing in the treatment of major depressive disorder: results of a randomized, double-blind clinical trial BMC Psychiatry Depression Pharmacogenetics Precision medicine Antidepressant response Randomized clinical trial |
author_facet |
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 AB-GEN Collaborative Group José M. Menchón |
author_sort |
Víctor Pérez |
title |
Efficacy of prospective pharmacogenetic testing in the treatment of major depressive disorder: results of a randomized, double-blind clinical trial |
title_short |
Efficacy of prospective pharmacogenetic testing in the treatment of major depressive disorder: results of a randomized, double-blind clinical trial |
title_full |
Efficacy of prospective pharmacogenetic testing in the treatment of major depressive disorder: results of a randomized, double-blind clinical trial |
title_fullStr |
Efficacy of prospective pharmacogenetic testing in the treatment of major depressive disorder: results of a randomized, double-blind clinical trial |
title_full_unstemmed |
Efficacy of prospective pharmacogenetic testing in the treatment of major depressive disorder: results of a randomized, double-blind clinical trial |
title_sort |
efficacy of prospective pharmacogenetic testing in the treatment of major depressive disorder: results of a randomized, double-blind clinical trial |
publisher |
BMC |
series |
BMC Psychiatry |
issn |
1471-244X |
publishDate |
2017-07-01 |
description |
Abstract 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. Trial registration European Clinical Trials Database 2013-002228-18 , registration date September 16, 2013; ClinicalTrials.gov NCT02529462 , retrospectively registered: August 19, 2015. |
topic |
Depression Pharmacogenetics Precision medicine Antidepressant response Randomized clinical trial |
url |
http://link.springer.com/article/10.1186/s12888-017-1412-1 |
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doaj-d5844f200b4f4f299135845fb3c486c52020-11-25T02:32:52ZengBMCBMC Psychiatry1471-244X2017-07-0117111310.1186/s12888-017-1412-1Efficacy of prospective pharmacogenetic testing in the treatment of major depressive disorder: results of a randomized, double-blind clinical trialVíctor Pérez0Ariana Salavert1Jordi Espadaler2Miquel Tuson3Jerónimo Saiz-Ruiz4Cristina Sáez-Navarro5Julio Bobes6Enrique Baca-García7Eduard Vieta8José M. Olivares9Roberto Rodriguez-Jimenez10José M. Villagrán11Josep Gascón12Josep Cañete-Crespillo13Montse Solé14Pilar A. Saiz15Ángela Ibáñez16Javier de Diego-Adeliño17AB-GEN Collaborative GroupJosé M. Menchón18Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM)AB-Biotics, S. AAB-Biotics, S. AAB-Biotics, S. ACentro de Investigación Biomédica en Red de Salud Mental (CIBERSAM)Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM)Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM)Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM)Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM)Department of Psychiatry, Hospital Álvaro Cunqueiro, Complejo Hospitalario Universitario de Vigo, Instituto Biomédico Galicia SurCentro de Investigación Biomédica en Red de Salud Mental (CIBERSAM)Psychiatric Hospitalization Unit, Hospital General de Jerez de la FronteraPsychiatric Unit, Hospital Universitari Mútua TerrassaMental Health Department, Hospital de Mataró, Consorci Sanitari del MaresmeCentro de Investigación Biomédica en Red de Salud Mental (CIBERSAM)Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM)Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM)Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM)Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM)Abstract 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. Trial registration European Clinical Trials Database 2013-002228-18 , registration date September 16, 2013; ClinicalTrials.gov NCT02529462 , retrospectively registered: August 19, 2015.http://link.springer.com/article/10.1186/s12888-017-1412-1DepressionPharmacogeneticsPrecision medicineAntidepressant responseRandomized clinical trial |