Efficacy of agomelatine (25 mg/day with potential adjustment to 50 mg) given orally on rest/activity circadian rhythms in outpatients with Major Depressive Disorder. A randomized, double-blind international study with parallel groups versus sertraline (50 mg/day with potential adjustment to 100 mg). Six-week treatment plus optional continuation for 18 weeks.
- Conditions
- Major Depressive DisorderMedDRA version: 3.3Level: P.T.Classification code 10025453
- Registration Number
- EUCTR2004-004009-10-ES
- Lead Sponsor
- Institut de Recherches Internationales Servier
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 300
Selection criteria :
Demographic criteria : male or female out-patients, aged of 18 to 60 years (both inclusive),
Diagnostic criteria :
- Fulfilling DSM-IV-TR criteria for Major Depressive Disorder, single or recurrent episode of moderate or severe intensity:
. With or without melancholic features according to DSM-IV-TR criteria,
. Without seasonal pattern according to DSM-IV-TR criteria,
. Without psychotic features,
. Without post partum onset for the current episode,
. Without catatonic features,
. Current episode > or = 4 weeks,
- Hamilton Depression Rating Scale :
. HAM-D 17 items total score greater than or equal to 22,
. Sum of HAM-D item 5 Insomnia: middle of the night” + item 6 Insomnia: early hours of the morning” greater than or equal to 3,
- Requiring an antidepressant treatment,
- Hospital Anxiety Depression Scale : HAD completed by the patient to characterize the anxiety condition and to make sure that depression predominates on anxiety, if any.
- Barratt Impulsiveness Scale : BIS-11 completed by the patient to measure impulsivenes.
- Patient agrees to wear an actimeter and to fill in a sleep-wake diary during the seven continuous weeks, starting at the selection visit.
The safety examination of the patients includes the following tests and will check for the absence of any abnormalities likely to interfere with the study conduct or evaluations:
- prescription of laboratory tests (biochemistry including T3, T4, TSH and pregnancy test, haematology and benzodiazepines tests). Results must be available for the inclusion visit.
- Prescription of a 12-lead ECG. Results and ECG tracing must be available for the inclusion visit.
Inclusion criteria :
- The investigator will check that the selection criteria are still fulfilled, especially Diagnostic criteria”,
- HAM-D 17-items total score still greater than or equal to 22,
- HAM-D item 3 (suicide) minor than or equal to 2,
- HAM-D decrease (if any) between ASSE and W0 minor than or equal to 20%,
- Sum of HAM-D items 5+6 greater than or equal to 3,
- Sum of items H1+H2+H5+H6+H7+H8+H10+H13 (core of depression + 2 items on sleep 5 and 6) of HAM-D 17-items greater than or equal to 55% of HAM-D 17-items total score, checked by IVRS,
- CGI item 1 Severity of illness” greater than or equal to 4 (moderately to severely ill).
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
Demographic and general non-selection criteria :
Women of childbearing potential without effective contraception.
Medical and therapeutic non-selection criteria :
Psychiatric criteria - Other Depressive Disorders :
- All types of depression other than Major Depressive Disorder :
. Bipolar Disorder I and II,
. Double Depression (Major Depressive Disorder superimposed on Dysthymic Disorder according to DSM-IV-TR),
. Chronic Depression (duration of the episode longer than 2 years),
. Schizoaffective Disorder Depressive or Bipolar type,
. Dysthymic Disorder according to DSM-IV criteria (checked by the M.I.N.I.)
- Depression onset within 3 months after a stroke.
- Current depressive episode having not responded to 2 different previous antidepressant treatments of at least 4 weeks at an appropriate dose.
- Previous non responders to sertraline or hypersensitivity to sertraline.
- Previous non responders to agomelatine (for patients having participated in a previous clinical trial).
- Marked suicidal intent and/or known suicidal tendencies for the current episode defined as HAM-D item 3 score > 2 and the investigator's opinion based on the patient’s medical history, previous suicide attempts, quality of social and familial support within the last 6 months.
- Patient treated with ECT (Electro Convulsive Therapy) within the last 3 months before selection or requiring ECT at present (according to investigator’s clinical judgement).
- Insight-oriented (psychoanalysis) and other structured psychotherapy (interpersonal therapy, cognitive behavioural therapy) started within 3 months before inclusion.
- Light-therapy started within 2 weeks before inclusion.
Psychiatric criteria - Other psychiatric conditions according to DSM-IV:
- Anxiety disorders according to DSM-IV criteria (checked by the M.I.N.I.).
. Current Panic Disorder,
. Obsessive Compulsive Disorder,
. Post Traumatic Stress Disorder,
. Acute Stress Disorder.
- Patients with acute or chronic psychosis.
- Patients with antisocial, borderline or histrionic personality disorders according to DSM IV-TR criteria.
- Patients with a severe personality disorder other than antisocial, borderline or histrionic personality disorders and prone to interfere with the evaluation of the study according to the investigator’s judgement.
- Delirium or dementia according to DSM-IV-TR.
Sleep Disorders :
- Known Obstructive Sleep Apnea Syndrome previously diagnosed and not treated.
- Restless legs syndrome.
- Shift workers.
- Transmeridian flight (greater than or equal to 3 time zones) in the past 10 days before inclusion or planned in the first 6 weeks of the study.
Non-inclusion criteria :
- Any clinically relevant abnormality detected during the physical examination or the laboratory tests, and likely to interfere with the conduct of the study or with the evaluations, especially:
. Hepatic failure : gGT or transaminases > than 3 times the upper limit,
. Renal failure : creatinin > 150 mmol/l,
. Positive beta hCG for women,
. Positive drug screening for benzodiazepines.
- Clinically relevant ECG abnormality, according to the investigator’s opinion.
- Treatment with a forbidden drug present at inclusion.
- IVRS refusal, if inclusion criteria not respected.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method