The Early Medication Change (EMC) Trial

Official Title: “Randomised Clinical Trial Comparing Early Medication Change (EMC) Strategy With Treatment as Usual (TAU) in Patients With Major Depressive Disorder - the EMC Trial”

The EMC trial investigates for the first time prospectively whether Major Depression Disorder patients with non-improvement after 14 days of antidepressive treatment with EMC are more likely to become remitters compared to patients treated according to current guidelines, i.e., with a medication change after 28 days of treatment in case of non-response.

Intervention(s) in this Clinical Trial

• Drug: Escitalopram, venlafaxine, lithium
  • oral application, highest tolerable dose, once daily
• Drug: Escitalopram, venlafaxine
  • oral application, highest tolerable dose, once daily

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: EMC (Early Medication Change)
• Active Comparator: TAU (Therapy As Usual)

Primary Measures

• Remission from MDD on day 56, defined as a HAMD17 sum score ≤ 7, in non-improvers on day 14
  • Time Frame: 8 weeks
    Safety Issue?: No

Secondary Measures

• Response, defined as a HAMD17 sum score decrease ≥50% on day 56
  • Time Frame: 8 weeks
    Safety Issue?: No
• Absolute change of HAMD17 sum score
  • Time Frame: 8 weeks
    Safety Issue?: No
• Remission defined as IDS score ≤ 11 on day 56
  • Time Frame: 8 weeks
    Safety Issue?: No
• Response defined as IDS score decrease ≥50% on day 56
  • Time Frame: 8 weeks
    Safety Issue?: No
• Absolute change in SF12 subscales "physical component score" and "mental component score"
  • Time Frame: 8 weeks
    Safety Issue?: No
• Remission from MDD, defined as a HAMD17 sum score ≤ 7 on day 56 (subgroups of improvers on day 14)
  • Time Frame: 8 weeks
    Safety Issue?: No
• Time to remission and time to response according to IDS and HAMD17
  • Time Frame: 8 weeks
    Safety Issue?: No
• Occurrence of adverse events, UKU ratings at all visits, relevant laboratory data and deviations from normal ECG
  • Time Frame: 8 weeks
    Safety Issue?: Yes

Inclusion Criteria:

• Major Depressive Disorder (MDD), first episode or recurrent, according to DSM‐IV
• HAMD17 score of ≥18 pts.
• Age between 18 and 65 years and age ≤ 60 years at the time of the first depressive episode
• Ability of subject to understand character and individual consequences of clinical trial
• Signed and dated informed consent of the subject must be available before start of any specific trial procedures.

Exclusion Criteria:

• Acute risk of suicide needing an intervention not comprised by protocol treatment (e.g. electroconvulsive therapy)
• Patients with a lifetime DSM‐IV diagnosis of dementia, schizophrenia, schizoaffective disorder, bipolar disorder
• Patients with a current DSM‐IV diagnosis of posttraumatic stress disorder, obsessive‐compulsive disorder, anxiety disorder, or eating disorder and the requirement of a treatment not comprised by protocol treatment
• Patients with DSM‐IV substance dependency requiring acute detoxification
• Depression due to organic brain disorder, e.g. Multiple Sclerosis and Parkinson's
• Disease
• Women who are pregnant, breastfeeding or planning to become pregnant during the trial
• Women who are not sterile by surgery or for more than two years postmenopausal or women with childbearing potential who not practicing a medically accepted contraception during trial
• Patients currently taking antidepressant medication, which has been started within the 2‐4 weeks prior to study begin and a continuation of this antidepressant medication is clinically indicated
• A clear history of non‐response to an adequate treatment trial in the current major depressive episode to any protocol antidepressant. A "clear history of non‐response" has to be assumed, when the following criteria are fulfilled:
• ad Escitalopram: Treatment with a mDDD ≥ 15 mg/d for 4 weeks or CPL 15‐80 ng/ml for four weeks without response, i.e. a symptom reduction ≥ 50% between start and end of treatment.
• ad Venlafaxine: Treatment with a mDDD ≥ 300 mg/d for 4 weeks or CPL 195‐400 ng/ml for four weeks without response, i.e. a symptom reduction ≥ 50% between start and end of treatment;
• ad Lithium: Treatment with CPL 0.6‐0.8 mmol Li+ for four weeks without response, i.e. a symptom reduction ≥ 50% between start and end of treatment
• History of medical or psychological condition, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or render the patient at high risk from treatment complications
• History of hypersensitivity to the investigational medicinal product or to any drug with similar chemical structure or to any excipient present in the pharmaceutical form of the investigational medicinal product
• Clinically significant or unstable medical or surgical condition that may preclude safe and complete study participation. Such conditions may include gastrointestinal, cardiovascular, vascular disease, pulmonary/respiratory, hepatic impairment, renal, metabolic diseases, endocrinological, neurological, immune‐deficiency, hematopoietic disease, or malignancies as determined by medical history, physical examination, or laboratory tests
• Participation in other clinical trials during the present clinical trial or within the last 6 months
• Medical or psychological condition that would not permit signing of informed consent

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 65 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Johannes Gutenberg University Mainz Other

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00974155

Study ID Number: 2008-016

ClinicalTrials.gov Identifier: NCT00974155

Health Authority: Germany: Federal Institute for Drugs and Medical Devices