000161984 001__ 161984 000161984 005__ 20251207075112.0 000161984 0247_ $$2doi$$a10.1192/bjp.2025.13 000161984 0248_ $$2sideral$$a144641 000161984 037__ $$aART-2025-144641 000161984 041__ $$aeng 000161984 100__ $$aPérez, Víctor 000161984 245__ $$aThe 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 000161984 260__ $$c2025 000161984 5203_ $$aBackground 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. 000161984 536__ $$9info:eu-repo/grantAgreement/ES/ISCIII/FIS/EC07-90244 000161984 540__ $$9info:eu-repo/semantics/openAccess$$aAll rights reserved$$uhttp://www.europeana.eu/rights/rr-f/ 000161984 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion 000161984 700__ $$aPuigdemont, Dolors 000161984 700__ $$ade Diego-Adeliño, Javier 000161984 700__ $$aElices, Matilde 000161984 700__ $$aLeal, Itziar 000161984 700__ $$aCabello, Maria 000161984 700__ $$aRodriguez-Jimenez, Roberto 000161984 700__ $$aÁlvarez-Mon, Miguel Ángel 000161984 700__ $$aGarcía-Fernández, Lorena 000161984 700__ $$aAguilar García-Iturrospe, Eduardo José 000161984 700__ $$aEscartí, Maria José 000161984 700__ $$aMontejo, Angel Luis 000161984 700__ $$aMontes, José Manuel 000161984 700__ $$aUsall, Judith 000161984 700__ $$aGallego-Nogueras, Ascensión 000161984 700__ $$aLujan, Elena 000161984 700__ $$aLópez-Carrilero, Raquel 000161984 700__ $$aGonzález-Pinto, Ana 000161984 700__ $$aOrtiz-Jauregui, Agurtzane 000161984 700__ $$aBlanch, Jordi 000161984 700__ $$aUrretavizcaya, Mikel 000161984 700__ $$aColom, Francesc 000161984 700__ $$aGarcía-Campayo, Javier$$uUniversidad de Zaragoza 000161984 700__ $$aAyuso-Mateos, José Luis 000161984 7102_ $$14009$$2680$$aUniversidad de Zaragoza$$bDpto. Psicología y Sociología$$cÁrea Person.Eval.Trat.Psicoló. 000161984 773__ $$g(2025), 8$$pBr. j. psychiatry$$tBRITISH JOURNAL OF PSYCHIATRY$$x0007-1250 000161984 8564_ $$s631960$$uhttps://zaguan.unizar.es/record/161984/files/texto_completo.pdf$$yVersión publicada$$zinfo:eu-repo/date/embargoEnd/2025-12-06 000161984 8564_ $$s3249387$$uhttps://zaguan.unizar.es/record/161984/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada$$zinfo:eu-repo/date/embargoEnd/2025-12-06 000161984 909CO $$ooai:zaguan.unizar.es:161984$$particulos$$pdriver 000161984 951__ $$a2025-10-17-14:16:47 000161984 980__ $$aARTICLE