The Early Medication Change (EMC) Trial

Study Overview
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Brief Summary
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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.

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

Conditions
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Depression

Intervention / Treatment
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* Drug: Escitalopram, venlafaxine, lithium
* Drug: Escitalopram, venlafaxine


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: EMC (Early Medication Change)<br> | Drug: Escitalopram, venlafaxine, lithium<br>* oral application, highest tolerable dose, once daily<br>|
| Active Comparator: TAU (Therapy As Usual)<br> | Drug: Escitalopram, venlafaxine<br>* oral application, highest tolerable dose, once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Remission from MDD on day 56, defined as a HAMD17 sum score ≤ 7, in non-improvers on day 14 (n=192) |  | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response, defined as a HAMD17 sum score decrease ≥50% on day 56 |  | 8 weeks | 
| Absolute change of HAMD17 sum score |  | 8 weeks | 
| Remission defined as IDS score ≤ 11 on day 56 |  | 8 weeks | 
| Response defined as IDS score decrease ≥50% on day 56 |  | 8 weeks | 
| Absolute change in SF12 subscales physical component score and mental component score |  | 8 weeks | 
| Remission from MDD, defined as a HAMD17 sum score ≤ 7 on day 56 (subgroups of improvers on day 14) |  | 8 weeks | 
| Time to remission and time to response according to IDS and HAMD17 |  | 8 weeks | 
| Occurrence of adverse events, UKU ratings at all visits, relevant laboratory data and deviations from normal ECG |  | 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Major, Depression, Disorder