Efficacy of prospective pharmacogenetic testing in the treatment of major depressive disorder: Results of a randomized, double-blind clinical trial
Author
Pérez, Víctor; Salavert, Ariana; Espadaler, Jordi; Tuson, Miquel; Saiz-Ruiz, Jerónimo; Sáez-Navarro, Cristina; Bobes, Julio; Baca García, Enrique; Vieta, Eduard; Olivares, José M.; Rodriguez-Jiménez, Roberto; Villagrán, José M.; Gascón, Josep; Cañete-Crespillo, Josep; Solé, Montse; Saiz, Pilar A.; Ibáñez, Ángela; Diego-Adeliño, Javier de; AB-GEN Collaborative Group; Menchón, José M.Entity
UAM. Departamento de Psiquiatría; Instituto de Investigación Sanitaria Fundación Jiménez Díaz (IIS-FJD)Publisher
BioMed Central Ltd.Date
2017-07-14Citation
10.1186/s12888-017-1412-1
BMC Psychiatry 17.1 (2017): 250-1
ISSN
1471-244XDOI
10.1186/s12888-017-1412-1Funded by
This work was supported by the Spanish Centre for Industrial Technological Development (Centro para el Desarrollo Tecnológico Industrial, CDTI; IDI-20130958) and the Spanish Ministry of Economy and Competitiveness PTQ-11-05076; PTQ- 11-04914; INC-FPGS-2011-2223; INC-FPGS-2011-2224. The funding agency had no role in the development of the study design, collection of data, manuscript development, or the decision to submit this manuscript for publication. The study also received funding support from private investors (Mr. Luis Sánchez-Lafuente and Mr. Sergi Audivert) as well as from Almirall SA (Barcelona, Spain). AB-Biotics as sponsor participated in the design, analysis and interpretation of the studyProject
Gobierno de España. IDI-20130958; Gobierno de España. PTQ-11-05076; Gobierno de España. PTQ- 11-04914; Gobierno de España. INC-FPGS-2011-2223; Gobierno de España. INC-FPGS-2011-2224Editor's Version
https://doi.org/10.1186/s12888-017-1412-1Subjects
Depression; Pharmacogenetics; Precision medicine; Antidepressant response; Randomized clinical trial; MedicinaRights
© The Author(s). 2017Abstract
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.
Files in this item
Google Scholar:Pérez, Víctor
-
Salavert, Ariana
-
Espadaler, Jordi
-
Tuson, Miquel
-
Saiz-Ruiz, Jerónimo
-
Sáez-Navarro, Cristina
-
Bobes, Julio
-
Baca García, Enrique
-
Vieta, Eduard
-
Olivares, José M.
-
Rodriguez-Jiménez, Roberto
-
Villagrán, José M.
-
Gascón, Josep
-
Cañete-Crespillo, Josep
-
Solé, Montse
-
Saiz, Pilar A.
-
Ibáñez, Ángela
-
Diego-Adeliño, Javier de
-
AB-GEN Collaborative Group
-
Menchón, José M.
This item appears in the following Collection(s)
Related items
Showing items related by title, author, creator and subject.