The DEPRE'5 study: pragmatic, multicentre, five-arm, parallel-group randomised controlled trial with blinded assessment to compare treatment strategies in major depression after a failed selective serotonin reuptake inhibitor treatment
Por:
Pérez V, Puigdemont D, de Diego-Adeliño J, Elices M, Leal I, Cabello M, Rodriguez-Jimenez R, Álvarez-Mon MÁ, García-Fernández L, Aguilar García-Iturrospe EJ, Escartí MJ, Montejo AL, Montes JM, Usall J, Gallego-Nogueras A, Lujan E, López-Carrilero R, González-Pinto A, Ortiz-Jauregui A, Jordi Blanch Andreu, Urretavizcaya M, Colom F, García-Campayo J and Ayuso-Mateos JL
Publicada:
1 nov 2025
Ahead of Print:
1 jun 2025
Resumen:
Background Selective serotonin reuptake inhibitors (SSRIs) are the first-line treatment for major depressive disorder (MDD), but initial outcomes can be modest. Aims To compare SSRI dose optimisation with four alternative second-line strategies in MDD patients unresponsive to an SSRI. Method Of 257 participants, 51 were randomised to SSRI dose optimisation (SSRI-Opt), 46 to lithium augmentation (SSRI+Li), 48 to nortriptyline combination (SSRI+NTP), 55 to switch to venlafaxine (VEN) and 57 to problem-solving therapy (SSRI+PST). Primary outcomes were week-6 response/remission rates, assessed by blinded evaluators using the 17-item Hamilton Depression Rating Scale (HDRS-17). Changes in HDRS-17 scores, global improvement and safety outcomes were also explored. EudraCT No. 2007-002130-11. Results Alternative second-line strategies led to higher response (28.2% v. 14.3%, odds ratio = 2.36 [95% CI 1.0-5.6], p = 0.05) and remission (16.9% v. 12.2%, odds ratio = 1.46, [95% CI 0.57-3.71], p = 0.27) rates, with greater HDRS-17 score reductions (-2.6 [95% CI -4.9 to -0.4], p = 0.021]) than SSRI-Opt. Significant/marginally significant effects were only observed in both response rates and HDRS-17 decreases for VEN (odds ratio = 2.53 [95% CI 0.94-6.80], p = 0.067; HDRS-17 difference: -2.7 [95% CI -5.5 to 0.0], p = 0.054) and for SSRI+PST (odds ratio = 2.46 [95% CI 0.92 to 6.62], p = 0.074; HDRS-17 difference: -3.1 [95% CI -5.8 to -0.3], p = 0.032). The SSRI+PST group reported the fewest adverse effects, while SSRI+NTP experienced the most (28.1% v. 75%; p < 0.01), largely mild. Conclusions Patients with MDD and insufficient response to SSRIs would benefit from any other second-line strategy aside from dose optimisation. With limited statistical power, switching to venlafaxine and adding psychotherapy yielded the most consistent results in the DEPRE'5 study.
Filiaciones:
Pérez V:
Instituto de Salud Mental, Hospital del Mar, Barcelona, Spain
Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain
Department of Medicine and Life Sciences, Universitat Pompeu Fabra (UPF), Barcelona, Spain
Centro de Investigación Biomédica en Red (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain
Puigdemont D:
Department of Psychiatry and Legal Medicine, Universitat Autònoma de Barcelona (UAB), Barcelona, Spain
Psychiatric Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
Sant Pau Mental Health, Institut de Recerca Sant Pau (IR Sant Pau), Barcelona, Spain
Centro de Investigación Biomédica en Red (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain
de Diego-Adeliño J:
Department of Psychiatry and Legal Medicine, Universitat Autònoma de Barcelona (UAB), Barcelona, Spain
Psychiatric Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
Sant Pau Mental Health, Institut de Recerca Sant Pau (IR Sant Pau), Barcelona, Spain
Centro de Investigación Biomédica en Red (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain
Elices M:
Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain
Centro de Investigación Biomédica en Red (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain
Leal I:
Instituto de Investigación Sanitaria del Hospital Universitario de La Princesa, IIS Princesa, Madrid, Spain
Department of Psychiatry, Universidad Autonoma de Madrid, Madrid, Spain
Centro de Investigación Biomédica en Red (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain
Cabello M:
Instituto de Investigación Sanitaria del Hospital Universitario de La Princesa, IIS Princesa, Madrid, Spain
Department of Psychiatry, Universidad Autonoma de Madrid, Madrid, Spain
Centro de Investigación Biomédica en Red (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain
Rodriguez-Jimenez R:
Facultad de Medicina, Universidad Complutense de Madrid (UCM), Madrid, Spain
Instituto de Investigación 12 de Octubre (i+12), Department of Psychiatry, Hospital Universitario 12 de Octubre, Madrid, Spain
Centro de Investigación Biomédica en Red (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain
Álvarez-Mon MÁ:
Departmento de Medicina y Especialidades Médicas, Universidad de Alcalá, Alcalá de Henares, Madrid, Spain
Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain
Departmento de Psiquiatría y Salud Mental, Hospital Universitario Infanta Leonor, Madrid, Spain
García-Fernández L:
Departamento de Medicina Clínica, Universidad Miguel HernándezAlicante, Spain
Servicio de Psiquiatría, Hospital Universitario de San JuanAlicante, Spain
Centro de Investigación Biomédica en Red (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain
Aguilar García-Iturrospe EJ:
Hospital Clínico Universitario de Valencia, Fundación Investigación Hospital Clínico de Valencia, INCLIVA, Valencia, Spain
Department of Medicine, University of Valencia, Valencia, Spain
Centro de Investigación Biomédica en Red (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain
Escartí MJ:
Hospital Clínico Universitario de Valencia, Fundación Investigación Hospital Clínico de Valencia, INCLIVA, Valencia, Spain
Department of Medicine, University CEU-UCH, Valencia, Spain
Centro de Investigación Biomédica en Red (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain
Montejo AL:
Servicio de Psiquiatría, Hospital Clínico Universitario, Universidad de Salamanca, Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, Spain
Montes JM:
Departmento de Medicina y Especialidades Médicas, Universidad de Alcalá, Alcalá de Henares, Madrid, Spain
Servicio de Psiquiatría, Hospital Universitario Ramón y Cajal, IRYCIS, Madrid, Spain
Centro de Investigación Biomédica en Red (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain
Usall J:
Parc sanitari Sant Joan de Déu, Institut de Recerca Sant Joan de Déu, Hospitalet de Llobregat, Spain
Gallego-Nogueras A:
Servicio de Psiquiatría, Hospital Clínico Universitario, Universidad de Salamanca, Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, Spain
Lujan E:
Servicio de Psiquiatría, Hospital Universitario del Sureste, Madrid, Spain
López-Carrilero R:
Parc sanitari Sant Joan de Déu, Institut de Recerca Sant Joan de Déu, Hospitalet de Llobregat, Spain
González-Pinto A:
Department Psychiatry, Hospital Universitario Alava, Vitoria, Spain
Centro de Investigación Biomédica en Red (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain
Ortiz-Jauregui A:
Department Psychiatry, Hospital Universitario Alava, Vitoria, Spain
Centro de Investigación Biomédica en Red (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain
Jordi Blanch Andreu:
Mental Health and Addiction Services, Hospital Universitari de Santa Maria de Lleida, Lleida, Spain
Department of Psychiatry and Psychology, Hospital Clinic of Barcelona, Barcelona, Spain
Clinical Sciences Department, University of Barcelona (UB), Barcelona, Spain
Centro de Investigación Biomédica en Red (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain
Urretavizcaya M:
Clinical Sciences Department, University of Barcelona (UB), Barcelona, Spain
Bellvitge University Hospital - ICS, Psychiatry, Bellvitge Biomedical Research Institute IDIBELL, Neurosciences Group-Psychiatry and Mental Health, L'Hospitalet de Llobregat, Spain
Centro de Investigación Biomédica en Red (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain
Colom F:
Instituto de Salud Mental, Hospital del Mar, Barcelona, Spain
Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain
Centro de Investigación Biomédica en Red (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain
García-Campayo J:
Institute of Health Research of Aragon (IIS Aragón), Miguel Servet University Hospital, Zaragoza, Spain
Research Network on Chronicity, Primary Care and Health Promotion (RICAPPS), Zaragoza, Spain
Psychiatry Department, Faculty of Medicine, University of Zaragoza, Zaragoza, Spain
Ayuso-Mateos JL:
Instituto de Investigación Sanitaria del Hospital Universitario de La Princesa, IIS Princesa, Madrid, Spain
Department of Psychiatry, Universidad Autonoma de Madrid, Madrid, Spain
Centro de Investigación Biomédica en Red (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain
Green Submitted, hybrid
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