{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T03:00:10Z","timestamp":1785207610899,"version":"3.55.0"},"reference-count":37,"publisher":"Royal College of Psychiatrists","issue":"5","license":[{"start":{"date-parts":[[2025,6,18]],"date-time":"2025-06-18T00:00:00Z","timestamp":1750204800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["cambridge.org"],"crossmark-restriction":true},"short-container-title":["Br J Psychiatry"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:sec id=\"S0007125025000133_as1\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Selective serotonin reuptake inhibitors (SSRIs) are the first-line treatment for major depressive disorder (MDD), but initial outcomes can be modest.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"S0007125025000133_as2\">\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>To compare SSRI dose optimisation with four alternative second-line strategies in MDD patients unresponsive to an SSRI.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"S0007125025000133_as3\">\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"S0007125025000133_as4\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Alternative second-line strategies led to higher response (28.2%\n                      <jats:italic>v.<\/jats:italic>\n                      14.3%, odds ratio = 2.36 [95% CI 1.0\u20135.6],\n                      <jats:italic>p<\/jats:italic>\n                      = 0.05) and remission (16.9%\n                      <jats:italic>v.<\/jats:italic>\n                      12.2%, odds ratio = 1.46, [95% CI 0.57\u20133.71],\n                      <jats:italic>p<\/jats:italic>\n                      = 0.27) rates, with greater HDRS-17 score reductions (\u22122.6 [95% CI \u22124.9 to \u22120.4],\n                      <jats:italic>p<\/jats:italic>\n                      = 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\u20136.80],\n                      <jats:italic>p<\/jats:italic>\n                      = 0.067; HDRS-17 difference: \u22122.7 [95% CI \u22125.5 to 0.0],\n                      <jats:italic>p<\/jats:italic>\n                      = 0.054) and for SSRI+PST (odds ratio = 2.46 [95% CI 0.92 to 6.62],\n                      <jats:italic>p<\/jats:italic>\n                      = 0.074; HDRS-17 difference: \u22123.1 [95% CI \u22125.8 to \u22120.3],\n                      <jats:italic>p<\/jats:italic>\n                      = 0.032). The SSRI+PST group reported the fewest adverse effects, while SSRI+NTP experienced the most (28.1%\n                      <jats:italic>v.<\/jats:italic>\n                      75%;\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.01), largely mild.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"S0007125025000133_as5\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1192\/bjp.2025.13","type":"journal-article","created":{"date-parts":[[2025,6,18]],"date-time":"2025-06-18T08:08:17Z","timestamp":1750234097000},"page":"748-755","update-policy":"https:\/\/doi.org\/10.1017\/policypage","source":"Crossref","is-referenced-by-count":3,"title":["The DEPRE\u20195 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"],"prefix":"10.1192","volume":"227","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5825-2337","authenticated-orcid":false,"given":"V\u00edctor","family":"P\u00e9rez","sequence":"first","affiliation":[{"name":"Instituto de Salud Mental"},{"name":"Hospital del Mar Medical Research 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Published by Cambridge University Press on behalf of Royal College of Psychiatrists","name":"copyright","label":"Copyright","group":{"name":"copyright_and_licensing","label":"Copyright and Licensing"}},{"value":"This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (https:\/\/creativecommons.org\/licenses\/by\/4.0\/), which permits unrestricted re-use, distribution and reproduction, provided the original article is properly cited.","name":"license","label":"License","group":{"name":"copyright_and_licensing","label":"Copyright and Licensing"}},{"value":"This content has been made available to all.","name":"free","label":"Free to read"}]}}