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, Alvarez-Mon, MA, García-Fernández, L, García-Iturrospe, EJA, Escartí, MJ, Montejo, AL, Montes, JM, Usall, J, Gallego-Nogueras, A, Lujan, E, López-Carrilero, R, González-Pinto, A, Ortiz-Jauregui, A, Blanch, J, Urretavizcaya, M, Colom, F, García-Campayo, J, 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:
Hosp Mar, Inst Salud Mental, Barcelona, Spain
Hosp Mar Med Res Inst IMIM, Barcelona, Spain
UPF, Dept Med & Life Sci, Barcelona, Spain
Inst Salud Carlos III, Ctr Invest Biomed Red CIBERSAM, Madrid, Spain
Puigdemont, D:
UAB, Dept Psychiat & Legal Med, Barcelona, Spain
Inst Salud Carlos III, Ctr Invest Biomed Red CIBERSAM, Madrid, Spain
Hosp Santa Creu & Sant Pau, Barcelona, Spain
Inst Recerca St Pau IR ST PAU, St Pau Mental Hlth, Barcelona, Spain
de Diego-Adeliño, J:
UAB, Dept Psychiat & Legal Med, Barcelona, Spain
Inst Salud Carlos III, Ctr Invest Biomed Red CIBERSAM, Madrid, Spain
Hosp Santa Creu & Sant Pau, Barcelona, Spain
Inst Recerca St Pau IR ST PAU, St Pau Mental Hlth, Barcelona, Spain
Elices, M:
Hosp Mar Med Res Inst IMIM, Barcelona, Spain
Leal, I:
Hosp Univ La Princesa, Inst Invest Sanitaria, IIS Princesa, Madrid, Spain
Univ Autonoma Madrid, Dept Pscyhiat, Madrid, Spain
Cabello, M:
Hosp Univ La Princesa, Inst Invest Sanitaria, IIS Princesa, Madrid, Spain
Univ Autonoma Madrid, Dept Pscyhiat, Madrid, Spain
Rodriguez-Jimenez, R:
UCM, Fac Med, Madrid, Spain
Inst Invest 12 i 12, Dept Psychiat, Hosp Univ 12 Octubre, Madrid, Spain
Alvarez-Mon, MA:
Clínica Universidad de Navarra
García-Fernández, L:
Univ Miguel Hernandez, Dept Med Clin, Alicante, Spain
Hosp Univ San Juan Alicante, Serv Psiquiatria, Alacant, Spain
García-Iturrospe, EJA:
Hosp Clin Univ Valencia, Fdn Invest Hosp Clin Valencia, INCLIVA, Valencia, Spain
Univ Valencia, Dept Med, Valencia, Spain
Escartí, MJ:
Hosp Clin Univ Valencia, Fdn Invest Hosp Clin Valencia, INCLIVA, Valencia, Spain
Univ UCH CEU, Dept Med, Valencia, Spain
Montejo, AL:
Univ Salamanca, Hosp Clin Univ, Serv Psiquiatria, Inst Invest Biomed Salamanca IBSAL, Salamanca, Spain
Montes, JM:
Univ Alcala, Dept Med & Especialidades Med, Madrid, Spain
Hosp Univ Ramon & Cajal, Serv Psiquiatria, Madrird, Spain
Usall, J:
Inst Recerca St Joan Deu, Parc Sanitari Sant Joan de Deu, Lhospitalet De Llobregat, Spain
Gallego-Nogueras, A:
Univ Salamanca, Hosp Clin Univ, Serv Psiquiatria, Inst Invest Biomed Salamanca IBSAL, Salamanca, Spain
Lujan, E:
Hosp Univ Sureste, Serv Psiquiatria, Madrid, Spain
López-Carrilero, R:
Inst Recerca St Joan Deu, Parc Sanitari Sant Joan de Deu, Lhospitalet De Llobregat, Spain
González-Pinto, A:
Hosp Univ Alava, Dept Psychiat, Vitoria, Spain
Ortiz-Jauregui, A:
Hosp Univ Alava, Dept Psychiat, Vitoria, Spain
Blanch, J:
Hosp Univ Santa Maria, Mental Hlth & Addict Serv, Lleida, Spain
Hosp Clin Barcelona, Dept Psychiat & Psychol, Barcelona, Spain
Univ Barcelona UB, Clin Sci Dept, Barcelona, Spain
Urretavizcaya, M:
Univ Barcelona UB, Clin Sci Dept, Barcelona, Spain
Bellvitge Univ Hosp, ICS, Psychiat, Bellvitge Biomed Res Inst IDIBELL, Lhospitalet De Llobregat, Spain
Colom, F:
Hosp Mar, Inst Salud Mental, Barcelona, Spain
Hosp Mar Med Res Inst IMIM, Barcelona, Spain
García-Campayo, J:
Miguel Servet Univ Hosp, Inst Hlth Res Aragon IIS Aragon, Zaragoza, Spain
Res Network Chron Primary Care & Hlth Promot RICAP, Zaragoza, Spain
Univ Zaragoza, Fac Med, Psychiat Dept, Zaragoza, Spain
Ayuso-Mateos, JL:
Hosp Univ La Princesa, Inst Invest Sanitaria, IIS Princesa, Madrid, Spain
Univ Autonoma Madrid, Dept Pscyhiat, Madrid, Spain
Inst Ramon & Cajal Invest Sanitaria IRYCIS, Madrid, Spain
Hosp Univ Infanta Leonor, Departmento Psiquiatria & Salud Mental, Madrid, Spain
Green Submitted, hybrid
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