ESPION: EScitalopram PIndolol ONset of Action

Sponsor

Markus KOSEL (Other)

Overall Status

Terminated

CT.gov ID

NCT01219686

Collaborator

University Hospital, Geneva (Other), University of Lausanne Hospitals (Other), University Hospital, Basel, Switzerland (Other), H. Lundbeck A/S (Industry)

Enrollment

Location

Arms

Duration (Months)

0.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Unipolar Depression	Drug: escitalopram, pindolol Drug: escitalopram Drug: escitalopram	Phase 2/Phase 3

Detailed Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

18 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, 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

Study Start Date :

Oct 1, 2010

Actual Primary Completion Date :

Apr 1, 2013

Actual Study Completion Date :

Jun 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
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 Other Names: escitalopram/Cipralex pindolol/Viskene
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	Drug: escitalopram 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	Drug: escitalopram escitalopram 20 mg, p.o., once daily. Days 1-2: 10mg, days 3-42: 20 mg

Arm

Intervention/Treatment

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

Other Names:

escitalopram/Cipralex

pindolol/Viskene

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

Drug: escitalopram

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

Drug: escitalopram

escitalopram 20 mg, p.o., once daily. Days 1-2: 10mg, days 3-42: 20 mg

Outcome Measures

Primary Outcome Measures

MADRS score change between baseline and 2 weeks of treatment [day 14]
Differences in MADRS score changes (baseline-day 14) between treatment groups

Secondary Outcome Measures

Response/remission (MADRS) at 6 weeks [day 42]
% of patients with a given treatment which meet response/remssion criteria after 6 weeks of treatment, based on MADRS
Adverse events [See primary outcome measure]
Frequence of adverse events in treatment groups
Correlation of drug level of pindolol and/or escitalopram and clinical outcome (primary outcome) between treatment groups [Day 10]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

patients aged between 18 and 65 years old
patients suffering from major depression according to DSM-IV with a MADRS score of at least 25 and not treated by an antidepressant at the time of inclusion with the exception of non-responders to antidepressant for a period of at least 6 weeks or not tolerating an ongoing antidepressant necessitating a change of the antidepressant(excluding fluoxetine and irreversible MAOI)
informed consent

Exclusion criteria:

any other Axis I disorder excluding anxiety disorder not dominating the clinical picture, nicotine abuse
non-responders to escitalopram in the past
already taking pindolol
pregnancy and breast feeding
contraindication to one of the two treatments (medical conditions, drug treatments)
significant somatic comorbidity interfering with the study procedures
high risk of suicidality
women of childbearing age not having a safe means of contraception