Randomised clinical trial comparing early medication change (EMC) strategy with treatment as usual (TAU) in patients with Major Depressive Disorder- the EMC trial.
- Conditions
- F32.1F32.2F33.1F33.2Moderate depressive episodeSevere depressive episode without psychotic symptomsRecurrent depressive disorder, current episode moderateRecurrent depressive disorder, current episode severe without psychotic symptoms
Recruitment & Eligibility
- Status
- Complete
- Sex
- All
- Target Recruitment
- 928
Major Depressive Disorder (MDD), first episode or recurrent, according to DSM-IV
-A HAMD17 score of >=18 pts. (Rationale: Although there exist different cut-offs for mild to moderate depression varying between 13/14-17/18 pts., the cut-off of >=18 pts. is the most often used in clinical trials and assures the inclusion of at least moderately depressed patients).
-Age between 18 and 65 years and age <= 60 years at the time of the first depressive episode. (Rationale: This age range assures the inclusion of patients with early-onset depression in contrast to late-onset depression, for which different pathophysiological mechanisms have been suggested. In addition, the vast majority of studies on the predictive value of early improvement included patients aged <= 65 years).
-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.
-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 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 including Multiple Sclerosis and Parkinsons 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 (reliable contraception are systemic contraceptives (oral, implant, injection), diaphragm or condoms with spermicide, sexual abstinence).
-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 to 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 weeks 4 weeks or CPL 195-400 ng/ml for four weeks without response
-ad Lithium: Treatment with CPL 0.6-0.8 mmol Li+ for four weeks without response
-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.
Study & Design
- Study Type
- interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Remission from MDD, defined as a HAMD17 sum score <=7 on day 56, is the primary endpoint and will be analyzed only for non-improvers on day 14 (level 1 of the EMC Trial).
- Secondary Outcome Measures
Name Time Method - Response, defined as a HAMD17 sum score decrease >=50% on day 56<br>- Absolute change of HAMD17 sum score [day 56 -day 0]<br>- Remission and response, defined as a sum score <=11 on the 30-item Inventory of Depressive Symptomatology (IDS-C30) and 50% baseline score reduction, respectively, on day 56. <br>- Time to remission and time to response according to IDS and HAMD17<br>- Remission from MDD, defined as HAMD17 sum score <= 7 on day 56 (in subgroups of improvers on day 14 entering level 2 or level 3 of The EMC trial)<br>- Absolute change in SF-12 subscales physical component score and mental component score [day 56-day 0].<br>- Occurrence of Adverse Events, UKU ratings at all visits and relevant laboratory data (routine laboratory, therapeutic drug monitoring)