EScitalopram PIndolol ONset of Action (ESPION)
The main purpose of this study is to determine whether the antidepressant response of escitalopram 30mg/day or escitalopram 20mg/day + pindolol, a beta blocker, is different (faster) compared to a standard dose of escitalopram 20mg/day.
Drug: escitalopram, pindolol
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Antidepressant Effect of Escitalopram: Delay of Onset. Clinical Randomized Double-blinded Study With Three Parallel Treatment Groups (Escitalopram 20mg vs Escitalopram 30mg vs Escitalopram 20 mg + Pindolol 15 mg/Day|
- MADRS score change between baseline and 2 weeks of treatment [ Time Frame: day 14 ] [ Designated as safety issue: No ]Differences in MADRS score changes (baseline-day 14) between treatment groups
- Response/remission (MADRS) at 6 weeks [ Time Frame: day 42 ] [ Designated as safety issue: No ]% of patients with a given treatment which meet response/remssion criteria after 6 weeks of treatment, based on MADRS
- Adverse events [ Time Frame: See primary outcome measure ] [ Designated as safety issue: Yes ]Frequence of adverse events in treatment groups
- Correlation of drug level of pindolol and/or escitalopram and clinical outcome (primary outcome) between treatment groups [ Time Frame: Day 10 ] [ Designated as safety issue: No ]
|Study Start Date:||October 2010|
|Estimated Study Completion Date:||July 2014|
|Estimated Primary Completion Date:||October 2013 (Final data collection date for primary outcome measure)|
Experimental: escitalopram 20mg + pindolol 15mg
Days 1-2: escitalopram 10 mg + placebo, days 3-42: escitalopram 20mg + placebo Days 1-14: pindolol 15 mg, days 15-17: pindolol 7.5 mg
Drug: escitalopram, pindolol
escitalopram p.o., once daily, day 1-2: 10mg, days 3-42: 20mg pindolol p.o., twice daily 7.5 mg days 1-14, once daily 7.5 mg days 15-17
Active Comparator: Escitalopram 30 mg
Days 1-2: escitalopram 10 mg+ placebo, days 3-4 escitalopram 20 mg + placebo, days 5-42: escitalopram 30mg+ placebo
escitalopram p.o., once daily. days 1-2: 10 mg, days 3-4: 20 mg, days 5-42: 30 mg
Active Comparator: escitalopram 20 mg
days 1-2: escitalopram 10 mg+ placebo, days 3-42: escitalopram 20 mg + placebo
escitalopram 20 mg, p.o., once daily. Days 1-2: 10mg, days 3-42: 20 mg
Antidepressant drug therapy is the primary therapeutic treatment option in moderate to severe Major Depressive Disorder. However, clinically significant antidepressant response needs sustained treatment during weeks to months. Indeed, in the largest effectiveness study conducted to date (STAR*D study) involving nearly 3000 depressed outpatients, only about one third of those who ultimately responded did so after 6 weeks of drug treatment and for most patients longer treatment periods were necessary. This delay implies prolonged suffering for the patients and their families. By its antagonist action on the serotonin 1A receptor pindolol is hypothesized to reduce the down-regulation mechanisms of antidepressants. It is therefore expected that addition of pindolol to escitalopram will shorten the therapeutic response. Clinical and preclinical data indicate that escitalopram at 30 mg/day might be more effective and perhaps be associated with a faster onset of action than 20mg. For this purpose the speed of action will be compared between three blindly randomized samples:
- escitalopram 20mg per day + placebo
- escitalopram 30mg per day + placebo
- escitalopram 20mg per day + pindolol 15mg per day (two doses of 7.5mg during 14 days).
Subjects will be followed for 6 weeks. The dose of 15mg pindolol per day (during 14 days) is based on the optimal occupancy of the serotonin 1A receptor.
At inclusion all subjects will be assessed by a trained psychiatrist using the SCID I mood disorder part which is based on DSM IV criteria, and by means of the French version of the MINI. Severity of depression will be assessed using the MADRS clinician rated and self-report questionnaire, and the French version of the QIDS.
Each week subjects will be assessed using the two versions of the Montgomery-Asberg Depression Rating Scale (MADRS) and the HCL-32 a self-report questionnaire assessing hypomania.
It is planned to include 135 patients during the three years of the study duration resulting in 45 subjects in each group.
|Contact: Markus Kosel, MD-PhD||+41 22 305 45 firstname.lastname@example.org|
|Contact: Jessica Grept, Master clinical psychology||+41 22 305 46 email@example.com|
|Centre de Thérapies Breves (CTB), Secteur Jonction||Recruiting|
|Geneva, Switzerland, 1205|
|Contact: Othman SENTISSI EL IDRISSI, MD +41 22 809 82 30 O.Sentissi@hcuge.ch|
|Sub-Investigator: Chi TL NGuyen, MD|
|Principal Investigator:||Markus Kosel, MD-PhD||University Hospital, Geneva|