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Randomized controlled study of early medication change for non-improvers to antidepressant therapy in major depression – The EMC trial
Abstract Patients with Major Depressive Disorder (MDD) and no improvement after two weeks of antidepressant pharmacotherapy have a high risk of treatment failure. The aim of the study was to determine whether an early medication change (EMC) strategy is superior to a guideline-based treatment in MDD...
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| Published in: | European neuropsychopharmacology 2016-04, Vol.26 (4), p.705-716 |
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| creator | Tadić, André Wachtlin, Daniel Berger, Mathias Braus, Dieter F van Calker, Dietrich Dahmen, Norbert Dreimüller, Nadine Engel, Alice Gorbulev, Stanislav Helmreich, Isabella Kaiser, Anne-Katrin Kronfeld, Kai Schlicht, Konrad F Tüscher, Oliver Wagner, Stefanie Hiemke, Christoph Lieb, Klaus |
| description | Abstract Patients with Major Depressive Disorder (MDD) and no improvement after two weeks of antidepressant pharmacotherapy have a high risk of treatment failure. The aim of the study was to determine whether an early medication change (EMC) strategy is superior to a guideline-based treatment in MDD patients without improvement after two weeks of antidepressant pharmacotherapy. Eight-hundred-and-eighty-nine patients with MDD were enrolled, 879 patients received the SSRI escitalopram. Of those, 192 patients had no improvement, defined as a reduction of |
| doi_str_mv | 10.1016/j.euroneuro.2016.02.003 |
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The aim of the study was to determine whether an early medication change (EMC) strategy is superior to a guideline-based treatment in MDD patients without improvement after two weeks of antidepressant pharmacotherapy. Eight-hundred-and-eighty-nine patients with MDD were enrolled, 879 patients received the SSRI escitalopram. Of those, 192 patients had no improvement, defined as a reduction of <20% on the Hamilton Depression Rating Scale (HAMD-17) after 14 days of treatment, and were randomly assigned to open treatment with the EMC strategy ( n =97; venlafaxine XR for study days 15–56; in case of sustained non-improvement on day 28, lithium augmentation for days 29–56) or TAU ( n =95; escitalopram continuation; non-responders on day 28 were switched to venlafaxine XR for four weeks, i.e. days 29–56). The primary outcome was remission (HAMD-17≤7) after 8 weeks of treatment as assessed by blinded raters. Remission rates were 24% for EMC and 16% for TAU, which was not significantly different ( p =0.2056). Sensitivity analyses for the primary and secondary effectiveness endpoints consistently showed favorable results for patients randomized to EMC. The results confirm data from post-hoc analyses of clinical trials showing that early non-improvement identifies patients who likely need alternate interventions. However, the herein used two-step switch/augmentation strategy for this risk group was not more effective than the control intervention. Alternate strategies and other design aspects are discussed in order to support researchers addressing the same research question.</description><identifier>ISSN: 0924-977X</identifier><identifier>EISSN: 1873-7862</identifier><identifier>DOI: 10.1016/j.euroneuro.2016.02.003</identifier><identifier>PMID: 26899588</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Adolescent ; Adult ; Aged ; Antidepressant ; Antidepressive Agents - administration & dosage ; Antidepressive Agents - adverse effects ; Antidepressive Agents - therapeutic use ; Antidepressive Agents, Second-Generation - therapeutic use ; Citalopram - administration & dosage ; Citalopram - adverse effects ; Citalopram - therapeutic use ; Delayed-Action Preparations - therapeutic use ; Depressive Disorder, Treatment-Resistant - drug therapy ; Drug Therapy, Combination ; Early improvement ; Early Medical Intervention ; Female ; Guidelines ; Humans ; Internal Medicine ; Lithium - therapeutic use ; Major Depressive Disorder ; Male ; Middle Aged ; Pharmacotherapy ; Psychiatry ; RCT ; Treatment Outcome ; Venlafaxine Hydrochloride - administration & dosage ; Venlafaxine Hydrochloride - adverse effects ; Venlafaxine Hydrochloride - therapeutic use ; Young Adult</subject><ispartof>European neuropsychopharmacology, 2016-04, Vol.26 (4), p.705-716</ispartof><rights>Elsevier B.V. and ECNP</rights><rights>2016 Elsevier B.V. and ECNP</rights><rights>Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c595t-ebd6861f6c82e7a93da1aa7e4659e75a8f335e139c5bf340f0a78cc1e7bc18f83</citedby><cites>FETCH-LOGICAL-c595t-ebd6861f6c82e7a93da1aa7e4659e75a8f335e139c5bf340f0a78cc1e7bc18f83</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26899588$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tadić, André</creatorcontrib><creatorcontrib>Wachtlin, Daniel</creatorcontrib><creatorcontrib>Berger, Mathias</creatorcontrib><creatorcontrib>Braus, Dieter F</creatorcontrib><creatorcontrib>van Calker, Dietrich</creatorcontrib><creatorcontrib>Dahmen, Norbert</creatorcontrib><creatorcontrib>Dreimüller, Nadine</creatorcontrib><creatorcontrib>Engel, Alice</creatorcontrib><creatorcontrib>Gorbulev, Stanislav</creatorcontrib><creatorcontrib>Helmreich, Isabella</creatorcontrib><creatorcontrib>Kaiser, Anne-Katrin</creatorcontrib><creatorcontrib>Kronfeld, Kai</creatorcontrib><creatorcontrib>Schlicht, Konrad F</creatorcontrib><creatorcontrib>Tüscher, Oliver</creatorcontrib><creatorcontrib>Wagner, Stefanie</creatorcontrib><creatorcontrib>Hiemke, Christoph</creatorcontrib><creatorcontrib>Lieb, Klaus</creatorcontrib><title>Randomized controlled study of early medication change for non-improvers to antidepressant therapy in major depression – The EMC trial</title><title>European neuropsychopharmacology</title><addtitle>Eur Neuropsychopharmacol</addtitle><description>Abstract Patients with Major Depressive Disorder (MDD) and no improvement after two weeks of antidepressant pharmacotherapy have a high risk of treatment failure. The aim of the study was to determine whether an early medication change (EMC) strategy is superior to a guideline-based treatment in MDD patients without improvement after two weeks of antidepressant pharmacotherapy. Eight-hundred-and-eighty-nine patients with MDD were enrolled, 879 patients received the SSRI escitalopram. Of those, 192 patients had no improvement, defined as a reduction of <20% on the Hamilton Depression Rating Scale (HAMD-17) after 14 days of treatment, and were randomly assigned to open treatment with the EMC strategy ( n =97; venlafaxine XR for study days 15–56; in case of sustained non-improvement on day 28, lithium augmentation for days 29–56) or TAU ( n =95; escitalopram continuation; non-responders on day 28 were switched to venlafaxine XR for four weeks, i.e. days 29–56). The primary outcome was remission (HAMD-17≤7) after 8 weeks of treatment as assessed by blinded raters. Remission rates were 24% for EMC and 16% for TAU, which was not significantly different ( p =0.2056). Sensitivity analyses for the primary and secondary effectiveness endpoints consistently showed favorable results for patients randomized to EMC. The results confirm data from post-hoc analyses of clinical trials showing that early non-improvement identifies patients who likely need alternate interventions. However, the herein used two-step switch/augmentation strategy for this risk group was not more effective than the control intervention. Alternate strategies and other design aspects are discussed in order to support researchers addressing the same research question.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Antidepressant</subject><subject>Antidepressive Agents - administration & dosage</subject><subject>Antidepressive Agents - adverse effects</subject><subject>Antidepressive Agents - therapeutic use</subject><subject>Antidepressive Agents, Second-Generation - therapeutic use</subject><subject>Citalopram - administration & dosage</subject><subject>Citalopram - adverse effects</subject><subject>Citalopram - therapeutic use</subject><subject>Delayed-Action Preparations - therapeutic use</subject><subject>Depressive Disorder, Treatment-Resistant - drug therapy</subject><subject>Drug Therapy, Combination</subject><subject>Early improvement</subject><subject>Early Medical Intervention</subject><subject>Female</subject><subject>Guidelines</subject><subject>Humans</subject><subject>Internal Medicine</subject><subject>Lithium - therapeutic use</subject><subject>Major Depressive Disorder</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Pharmacotherapy</subject><subject>Psychiatry</subject><subject>RCT</subject><subject>Treatment Outcome</subject><subject>Venlafaxine Hydrochloride - administration & dosage</subject><subject>Venlafaxine Hydrochloride - adverse effects</subject><subject>Venlafaxine Hydrochloride - therapeutic use</subject><subject>Young Adult</subject><issn>0924-977X</issn><issn>1873-7862</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><recordid>eNqNkkGP1CAYhonRuOPoX1COXlqhTAtcTDaTXTVZY6Jr4o0w9KtDbWEEukk97XHv_kN_iTQz7sHTXoDA-34feZ8PoVeUlJTQ5k1fwhS8W5ayyhclqUpC2CO0ooKzgoumeoxWRFabQnL-7Qw9i7EnhNaMyaforGqElLUQK3T3WbvWj_YXtNh4l4IfhnyMaWpn7DsMOgwzHqG1RifrHTZ77b4D7nzAzrvCjofgbyBEnDzWLtkWDgFizEec9hD0YcbW4VH32XB6W8r8uf2Nr_eALz5ucQpWD8_Rk04PEV6c9jX6enlxvX1fXH1692F7flWYWtapgF3biIZ2jREVcC1Zq6nWHDZNLYHXWnSM1UCZNPWuYxvSEc2FMRT4zlDRCbZGr491879_ThCTGm00MAzagZ-iolwSyTc5qAdIeU0bKbN4jfhRaoKPMUCnDsGOOsyKErUQU726J6YWYopUKhPLzpenJtMux3zv-4coC86PAsip3FgIKhoLzmQkAUxSrbcPaPL2vxpmsC4jHX7ADLH3U3A5dEVVzAb1ZRmcZW5oQ7JdEvYX17vFGA</recordid><startdate>20160401</startdate><enddate>20160401</enddate><creator>Tadić, André</creator><creator>Wachtlin, Daniel</creator><creator>Berger, Mathias</creator><creator>Braus, Dieter F</creator><creator>van Calker, Dietrich</creator><creator>Dahmen, Norbert</creator><creator>Dreimüller, Nadine</creator><creator>Engel, Alice</creator><creator>Gorbulev, Stanislav</creator><creator>Helmreich, Isabella</creator><creator>Kaiser, Anne-Katrin</creator><creator>Kronfeld, Kai</creator><creator>Schlicht, Konrad F</creator><creator>Tüscher, Oliver</creator><creator>Wagner, Stefanie</creator><creator>Hiemke, Christoph</creator><creator>Lieb, Klaus</creator><general>Elsevier B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>7TK</scope></search><sort><creationdate>20160401</creationdate><title>Randomized controlled study of early medication change for non-improvers to antidepressant therapy in major depression – The EMC trial</title><author>Tadić, André ; Wachtlin, Daniel ; Berger, Mathias ; Braus, Dieter F ; van Calker, Dietrich ; Dahmen, Norbert ; Dreimüller, Nadine ; Engel, Alice ; Gorbulev, Stanislav ; Helmreich, Isabella ; Kaiser, Anne-Katrin ; Kronfeld, Kai ; Schlicht, Konrad F ; Tüscher, Oliver ; Wagner, Stefanie ; Hiemke, Christoph ; Lieb, Klaus</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c595t-ebd6861f6c82e7a93da1aa7e4659e75a8f335e139c5bf340f0a78cc1e7bc18f83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Antidepressant</topic><topic>Antidepressive Agents - administration & dosage</topic><topic>Antidepressive Agents - adverse effects</topic><topic>Antidepressive Agents - therapeutic use</topic><topic>Antidepressive Agents, Second-Generation - therapeutic use</topic><topic>Citalopram - administration & dosage</topic><topic>Citalopram - adverse effects</topic><topic>Citalopram - therapeutic use</topic><topic>Delayed-Action Preparations - therapeutic use</topic><topic>Depressive Disorder, Treatment-Resistant - drug therapy</topic><topic>Drug Therapy, Combination</topic><topic>Early improvement</topic><topic>Early Medical Intervention</topic><topic>Female</topic><topic>Guidelines</topic><topic>Humans</topic><topic>Internal Medicine</topic><topic>Lithium - therapeutic use</topic><topic>Major Depressive Disorder</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Pharmacotherapy</topic><topic>Psychiatry</topic><topic>RCT</topic><topic>Treatment Outcome</topic><topic>Venlafaxine Hydrochloride - administration & dosage</topic><topic>Venlafaxine Hydrochloride - adverse effects</topic><topic>Venlafaxine Hydrochloride - therapeutic use</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tadić, André</creatorcontrib><creatorcontrib>Wachtlin, Daniel</creatorcontrib><creatorcontrib>Berger, Mathias</creatorcontrib><creatorcontrib>Braus, Dieter F</creatorcontrib><creatorcontrib>van Calker, Dietrich</creatorcontrib><creatorcontrib>Dahmen, Norbert</creatorcontrib><creatorcontrib>Dreimüller, Nadine</creatorcontrib><creatorcontrib>Engel, Alice</creatorcontrib><creatorcontrib>Gorbulev, Stanislav</creatorcontrib><creatorcontrib>Helmreich, Isabella</creatorcontrib><creatorcontrib>Kaiser, Anne-Katrin</creatorcontrib><creatorcontrib>Kronfeld, Kai</creatorcontrib><creatorcontrib>Schlicht, Konrad F</creatorcontrib><creatorcontrib>Tüscher, Oliver</creatorcontrib><creatorcontrib>Wagner, Stefanie</creatorcontrib><creatorcontrib>Hiemke, Christoph</creatorcontrib><creatorcontrib>Lieb, Klaus</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Neurosciences Abstracts</collection><jtitle>European neuropsychopharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tadić, André</au><au>Wachtlin, Daniel</au><au>Berger, Mathias</au><au>Braus, Dieter F</au><au>van Calker, Dietrich</au><au>Dahmen, Norbert</au><au>Dreimüller, Nadine</au><au>Engel, Alice</au><au>Gorbulev, Stanislav</au><au>Helmreich, Isabella</au><au>Kaiser, Anne-Katrin</au><au>Kronfeld, Kai</au><au>Schlicht, Konrad F</au><au>Tüscher, Oliver</au><au>Wagner, Stefanie</au><au>Hiemke, Christoph</au><au>Lieb, Klaus</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Randomized controlled study of early medication change for non-improvers to antidepressant therapy in major depression – The EMC trial</atitle><jtitle>European neuropsychopharmacology</jtitle><addtitle>Eur Neuropsychopharmacol</addtitle><date>2016-04-01</date><risdate>2016</risdate><volume>26</volume><issue>4</issue><spage>705</spage><epage>716</epage><pages>705-716</pages><issn>0924-977X</issn><eissn>1873-7862</eissn><abstract>Abstract Patients with Major Depressive Disorder (MDD) and no improvement after two weeks of antidepressant pharmacotherapy have a high risk of treatment failure. The aim of the study was to determine whether an early medication change (EMC) strategy is superior to a guideline-based treatment in MDD patients without improvement after two weeks of antidepressant pharmacotherapy. Eight-hundred-and-eighty-nine patients with MDD were enrolled, 879 patients received the SSRI escitalopram. Of those, 192 patients had no improvement, defined as a reduction of <20% on the Hamilton Depression Rating Scale (HAMD-17) after 14 days of treatment, and were randomly assigned to open treatment with the EMC strategy ( n =97; venlafaxine XR for study days 15–56; in case of sustained non-improvement on day 28, lithium augmentation for days 29–56) or TAU ( n =95; escitalopram continuation; non-responders on day 28 were switched to venlafaxine XR for four weeks, i.e. days 29–56). The primary outcome was remission (HAMD-17≤7) after 8 weeks of treatment as assessed by blinded raters. Remission rates were 24% for EMC and 16% for TAU, which was not significantly different ( p =0.2056). Sensitivity analyses for the primary and secondary effectiveness endpoints consistently showed favorable results for patients randomized to EMC. The results confirm data from post-hoc analyses of clinical trials showing that early non-improvement identifies patients who likely need alternate interventions. However, the herein used two-step switch/augmentation strategy for this risk group was not more effective than the control intervention. Alternate strategies and other design aspects are discussed in order to support researchers addressing the same research question.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>26899588</pmid><doi>10.1016/j.euroneuro.2016.02.003</doi><tpages>12</tpages></addata></record> |
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| subjects | Adolescent Adult Aged Antidepressant Antidepressive Agents - administration & dosage Antidepressive Agents - adverse effects Antidepressive Agents - therapeutic use Antidepressive Agents, Second-Generation - therapeutic use Citalopram - administration & dosage Citalopram - adverse effects Citalopram - therapeutic use Delayed-Action Preparations - therapeutic use Depressive Disorder, Treatment-Resistant - drug therapy Drug Therapy, Combination Early improvement Early Medical Intervention Female Guidelines Humans Internal Medicine Lithium - therapeutic use Major Depressive Disorder Male Middle Aged Pharmacotherapy Psychiatry RCT Treatment Outcome Venlafaxine Hydrochloride - administration & dosage Venlafaxine Hydrochloride - adverse effects Venlafaxine Hydrochloride - therapeutic use Young Adult |
| title | Randomized controlled study of early medication change for non-improvers to antidepressant therapy in major depression – The EMC trial |
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