The Effect of Patient and Investigator Expectation on the Efficacy of Escitalopram in the Treatment Depression

The Effect of Patient and Investigator Expectation on the Efficacy of Escitalopram in the Treatment of Patients With Major Depressive Disorder.

To evaluate the effect of visit number, patient expectation, and rater expectation of the efficacy of escitalopram treatment in fixed doses of 10 and 20mg, based on baseline severity in patients with MDD.

Study Overview

• Status: Completed
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Drug: Escitalopram

Detailed Description

This study is designed to determined if trial design, in the form of the frequency of patient contact (assessment visit numbers) has an effect on the efficacy outcome after 8-week treatment with escitalopram.

The placebo response is a major issue in clinical trials for psychiatric disorders-and especially in the management of depression. Possible contributing factors to this problem include diagnostic misclassification, issues concerning inclusion/exclusion criteria, outcome measures' lack of sensitivity to change, measurement errors, poor quality of data entry and verification, waxing and waning of the natural course of depression, regression toward the mean phenomenon, patient and clinician expectations about the trial, study design issues, non-specific therapeutic effects, and high attrition.

Over the past few decades, researchers have attempted to reduce the placebo effect in a variety of ways. Unfortunately, approaches with very little or no benefit have included restricting enrollment to selected populations, rater training, requirement of same rater, and placebo lead-in phases. Some benefits, although often marginal, have been derived from standardizing diagnostic procedures, managing clinicians' overestimation of change, simplification of study visits and assessments, minimizing nonspecific, therapeutic effects, extending trial duration, reducing number of sites, increasing the sensitivity of outcome measures, and reducing the number of treatment arms.

Thus far, there has been no attempt to develop new study designs aimed at reducing the placebo effect.

We are proposing a novel study design, suitable for doubleblind, trials in mood disorders. This design is aimed at characterizing and identifying both the overall placebo response rate and the sample size required for such

• Study Type: Interventional
• Enrollment (Actual): 52
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Israel
  • Bat-Yam, Israel, 59100
    • Abarbanel MHC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Outpatients, men and women between 18 and 65 years of age (both extremes included)
2. DSM IV-TR criteria for a current MDE lasting between 3 and 12 months
3. Baseline MADRS total score > 22

Exclusion Criteria:

1. WHO-5 total score > 13 or a score > 3 on any single item of the WHO-5 (not revealed to the investigator)
2. Other primary or co-primary psychiatric disorder which is more distressful for the patient than MDDD, as evaluated by investigator
3. Patients with any history of mania/bipolar I disorder
4. Patients using medications which are contraindicated with the use of escitalopram
5. Known contraindication for the use of citalopram or escitalopram
6. Patients that have not responded to 2 or more treatments with an adequate dose of an antidepressant for an adequate time
7. Patients receiving formal behaviour therapy, or systematic psychotherapy
8. Unable to understand or read Hebrew and give written informed consent
9. Prominent suicidal ideation > 5 on item 10 (suicidal thoughts) of the MADRS]
10. Alcohol or substance dependence in the past 6 months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Supported Escitalopram; Escitalopram, with assessment visits at baseline, and weeks 2, 4, 6 and 8	Drug: Escitalopram; Patients diagnosed with MDD and will fulfill the inclusion and exclusion criteria will start with escitalopram 10mg, according to the Summary of Product Characteristics. At week 2, patients with a baseline MADRS between 22 and 29 continue on 10mg, and patients with a baseline MADRS > 30 receive a fixed dose 20mg until the end of treatment.; Other Names: Cipralex, Lexapro
Active Comparator: Escitalopram; Escitalopram, with assessment visits at baseline, week 4 and week 8, and a safety visit at week 2	Drug: Escitalopram; Patients diagnosed with MDD and will fulfill the inclusion and exclusion criteria will start with escitalopram 10mg, according to the Summary of Product Characteristics. At week 2, patients with a baseline MADRS between 22 and 29 continue on 10mg, and patients with a baseline MADRS > 30 receive a fixed dose 20mg until the end of treatment.; Other Names: Cipralex, Lexapro

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sheehan Disability Scale	The Sheehan Disability Scale (Sheehan 1983) is a composite of three self-rated items designed to measure the extent to which three major sectors in the patient's life are impaired by panic, anxiety, phobic, or depressive symptoms. This scale has been used widely in psychopharmacology randomized controlled trials, particularly for panic disorder. This anchored visual analog scale uses spatiovisual, numeric, and verbal descriptive anchors simultaneously to assess disability across three domains: work, social life, and family life.	Change from baseline to study completion by week 8.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Montgomery Åsberg Depression Rating Scale	This is a 10-item checklist. Widely used in drug-treatment trials, mainly because of its particular sensitivity to treatment effects. Since there is a comparative lack of emphasis on somatic symptoms, the scale is useful for the assessment of depression in people with physical illness.	Change from baseline to study completion in week 8.

Collaborators and Investigators

• Sponsor: Abarbanel Mental Health Center
• Collaborators: H. Lundbeck A/S
• Investigators: Study Chair: Yehuda Baruch, MD, MHA, Abarbanel MHC, Israel.

Publications and helpful links

General Publications

• Gomeni R, Lavergne A, Merlo-Pich E. Modelling placebo response in depression trials using a longitudinal model with informative dropout. Eur J Pharm Sci. 2009 Jan 31;36(1):4-10. doi: 10.1016/j.ejps.2008.10.025. Epub 2008 Nov 8.

Study record dates

Study Major Dates

• Study Start: June 1, 2010
• Primary Completion (Actual): June 1, 2012
• Study Completion (Actual): October 1, 2012

Study Registration Dates

• First Submitted: June 22, 2015
• First Submitted That Met QC Criteria: June 22, 2015
• First Posted (Estimate): June 24, 2015

Study Record Updates

• Last Update Posted (Estimate): June 24, 2015
• Last Update Submitted That Met QC Criteria: June 22, 2015
• Last Verified: June 1, 2015

More Information

Terms related to this study

• Keywords: MDD; Placebo; Escitalopram
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder; Depressive Disorder, Major; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Parasympatholytics; Autonomic Agents; Peripheral Nervous System Agents; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Antidepressive Agents, Second-Generation; Antiparkinson Agents; Anti-Dyskinesia Agents; Citalopram; Dexetimide
• Other Study ID Numbers: Lu-Pl-001