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    <subfield code="g">(2025), 8</subfield>
    <subfield code="p">Br. j. psychiatry</subfield>
    <subfield code="t">BRITISH JOURNAL OF PSYCHIATRY</subfield>
    <subfield code="x">0007-1250</subfield>
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    <subfield code="a">2025-10-17-14:16:47</subfield>
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    <subfield code="a">Puigdemont, Dolors</subfield>
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    <subfield code="a">de Diego-Adeliño, Javier</subfield>
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    <subfield code="a">Elices, Matilde</subfield>
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  <datafield tag="700" ind1=" " ind2=" ">
    <subfield code="a">Leal, Itziar</subfield>
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    <subfield code="a">Cabello, Maria</subfield>
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    <subfield code="a">Rodriguez-Jimenez, Roberto</subfield>
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    <subfield code="a">Álvarez-Mon, Miguel Ángel</subfield>
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  <datafield tag="700" ind1=" " ind2=" ">
    <subfield code="a">García-Fernández, Lorena</subfield>
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  <datafield tag="700" ind1=" " ind2=" ">
    <subfield code="a">Aguilar García-Iturrospe, Eduardo José</subfield>
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  <datafield tag="700" ind1=" " ind2=" ">
    <subfield code="a">Escartí, Maria José</subfield>
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    <subfield code="a">Montejo, Angel Luis</subfield>
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  <datafield tag="700" ind1=" " ind2=" ">
    <subfield code="a">Montes, José Manuel</subfield>
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    <subfield code="a">Usall, Judith</subfield>
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    <subfield code="a">Gallego-Nogueras, Ascensión</subfield>
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    <subfield code="a">Lujan, Elena</subfield>
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    <subfield code="a">López-Carrilero, Raquel</subfield>
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    <subfield code="a">González-Pinto, Ana</subfield>
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    <subfield code="a">Ortiz-Jauregui, Agurtzane</subfield>
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    <subfield code="a">Blanch, Jordi</subfield>
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    <subfield code="a">Urretavizcaya, Mikel</subfield>
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    <subfield code="a">Colom, Francesc</subfield>
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    <subfield code="a">García-Campayo, Javier</subfield>
    <subfield code="u">Universidad de Zaragoza</subfield>
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  <datafield tag="700" ind1=" " ind2=" ">
    <subfield code="a">Ayuso-Mateos, José Luis</subfield>
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    <subfield code="9">info:eu-repo/semantics/openAccess</subfield>
    <subfield code="a">All rights reserved</subfield>
    <subfield code="u">http://www.europeana.eu/rights/rr-f/</subfield>
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  <datafield tag="710" ind1="2" ind2=" ">
    <subfield code="1">4009</subfield>
    <subfield code="2">680</subfield>
    <subfield code="a">Universidad de Zaragoza</subfield>
    <subfield code="b">Dpto. Psicología y Sociología</subfield>
    <subfield code="c">Área Person.Eval.Trat.Psicoló.</subfield>
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  <datafield tag="245" ind1=" " ind2=" ">
    <subfield code="a">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</subfield>
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  <datafield tag="024" ind1="7" ind2=" ">
    <subfield code="2">doi</subfield>
    <subfield code="a">10.1192/bjp.2025.13</subfield>
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  <datafield tag="024" ind1="8" ind2=" ">
    <subfield code="2">sideral</subfield>
    <subfield code="a">144641</subfield>
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    <subfield code="c">2025</subfield>
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  <datafield tag="520" ind1="3" ind2=" ">
    <subfield code="a">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 &lt; 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.</subfield>
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    <subfield code="a">info:eu-repo/semantics/article</subfield>
    <subfield code="v">info:eu-repo/semantics/publishedVersion</subfield>
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  <datafield tag="100" ind1=" " ind2=" ">
    <subfield code="a">Pérez, Víctor</subfield>
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  <datafield tag="037" ind1=" " ind2=" ">
    <subfield code="a">ART-2025-144641</subfield>
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  <datafield tag="041" ind1=" " ind2=" ">
    <subfield code="a">eng</subfield>
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