title: 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 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.
authors.affiliation: Department of Psychiatry and Psychotherapy, University Medical Centre Mainz, Germany. Electronic address: tadic@uni-mainz.de.
authors.forename: André
authors.initials: A
authors.lastname: Tadić
authors.affiliation: Interdisciplinary Centre for Clinical Trials (IZKS), University Medical Center Mainz, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Wachtlin
authors.affiliation: Department of Psychiatry and Psychotherapy of the University of Freiburg, Germany.
authors.forename: Mathias
authors.initials: M
authors.lastname: Berger
authors.affiliation: Department of Psychiatry and Psychotherapy, HELIOS Dr.-Horst-Schmidt-Hospital, Wiesbaden, Germany.
authors.forename: Dieter F
authors.initials: DF
authors.lastname: Braus
authors.affiliation: Department of Psychiatry and Psychotherapy of the University of Freiburg, Germany.
authors.forename: Dietrich
authors.initials: D
authors.lastname: van Calker
authors.affiliation: Department of Psychiatry and Psychotherapy, University Medical Centre Mainz, Germany; Hospital for Psychiatry and Psychotherapy, Katzenelnbogen, Germany.
authors.forename: Norbert
authors.initials: N
authors.lastname: Dahmen
authors.affiliation: Department of Psychiatry and Psychotherapy, University Medical Centre Mainz, Germany.
authors.forename: Nadine
authors.initials: N
authors.lastname: Dreimüller
authors.affiliation: Department of Psychiatry and Psychotherapy, University Medical Centre Mainz, Germany.
authors.forename: Alice
authors.initials: A
authors.lastname: Engel
authors.affiliation: Interdisciplinary Centre for Clinical Trials (IZKS), University Medical Center Mainz, Germany.
authors.forename: Stanislav
authors.initials: S
authors.lastname: Gorbulev
authors.affiliation: Department of Psychiatry and Psychotherapy, University Medical Centre Mainz, Germany.
authors.forename: Isabella
authors.initials: I
authors.lastname: Helmreich
authors.affiliation: Interdisciplinary Centre for Clinical Trials (IZKS), University Medical Center Mainz, Germany.
authors.forename: Anne-Katrin
authors.initials: AK
authors.lastname: Kaiser
authors.affiliation: Interdisciplinary Centre for Clinical Trials (IZKS), University Medical Center Mainz, Germany.
authors.forename: Kai
authors.initials: K
authors.lastname: Kronfeld
authors.affiliation: Department of Psychiatry and Psychotherapy, University Medical Centre Mainz, Germany.
authors.forename: Konrad F
authors.initials: KF
authors.lastname: Schlicht
authors.affiliation: Department of Psychiatry and Psychotherapy, University Medical Centre Mainz, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Tüscher
authors.affiliation: Department of Psychiatry and Psychotherapy, University Medical Centre Mainz, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Wagner
authors.affiliation: Department of Psychiatry and Psychotherapy, University Medical Centre Mainz, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Hiemke
authors.affiliation: Department of Psychiatry and Psychotherapy, University Medical Centre Mainz, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Lieb
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000928:Antidepressive Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D018687:Antidepressive Agents, Second-Generation / Q000627:therapeutic use; D015283:Citalopram / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003692:Delayed-Action Preparations / Q000627:therapeutic use; D061218:Depressive Disorder, Treatment-Resistant / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D061345:Early Medical Intervention; D005260:Female; D006801:Humans; D008094:Lithium / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D000069470:Venlafaxine Hydrochloride / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D000928:Antidepressive Agents; D018687:Antidepressive Agents, Second-Generation; D003692:Delayed-Action Preparations; D015283:Citalopram; D000069470:Venlafaxine Hydrochloride; D008094:Lithium
keywords: Antidepressant; Early improvement; Guidelines; Major Depressive Disorder; Pharmacotherapy; RCT