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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.

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Title: 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.
Authors: Pérez, Víctor (AUTHOR), Puigdemont, Dolors (AUTHOR), de Diego-Adeliño, Javier (AUTHOR), Elices, Matilde (AUTHOR), Leal, Itziar (AUTHOR), Cabello, Maria (AUTHOR), Rodriguez-Jimenez, Roberto (AUTHOR), Álvarez-Mon, Miguel Ángel (AUTHOR), García-Fernández, Lorena (AUTHOR), Aguilar García-Iturrospe, Eduardo José (AUTHOR), Escartí, Maria José (AUTHOR), Montejo, Angel Luis (AUTHOR), Montes, José Manuel (AUTHOR), Usall, Judith (AUTHOR), Gallego-Nogueras, Ascensión (AUTHOR), Lujan, Elena (AUTHOR), López-Carrilero, Raquel (AUTHOR), González-Pinto, Ana (AUTHOR), Ortiz-Jauregui, Agurtzane (AUTHOR), Blanch, Jordi (AUTHOR)
Source: British Journal of Psychiatry. Nov2025, Vol. 227 Issue 5, p748-755. 8p.
Subjects: Serotonin uptake inhibitors, Venlafaxine, Mental depression, Hamilton Depression Inventory, Randomized controlled trials, Therapeutic use of lithium, Problem-solving therapy, Therapeutics
Abstract: 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. [ABSTRACT FROM AUTHOR]
Copyright of British Journal of Psychiatry is the property of Cambridge University Press and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Psychology and Behavioral Sciences Collection
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  Data: The DEPRE&#39;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.
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  Data: &lt;searchLink fieldCode=&quot;JN&quot; term=&quot;%22British+Journal+of+Psychiatry%22&quot;&gt;British Journal of Psychiatry&lt;/searchLink&gt;. Nov2025, Vol. 227 Issue 5, p748-755. 8p.
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  Data: 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&#39;5 study. [ABSTRACT FROM AUTHOR]
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  Data: &lt;i&gt;Copyright of British Journal of Psychiatry is the property of Cambridge University Press and its content may not be copied or emailed to multiple sites without the copyright holder&#39;s express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.&lt;/i&gt; (Copyright applies to all Abstracts.)
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